Rare broncho-pulmonary arterial fistula in a healthy 9-year-old girl

Abstract

A 9-year-old previously well girl presented with multiple episodes of large volume haemoptysis and right sided consolidation. She continued to have haemoptysis despite intravenous antibiotics. CT chest suggested a right mainstem endobronchial lesion; this was not seen on bronchoscopy where an extensive blood clot was removed. Distal flexible bronchoscopy could not identify the source of bleeding. CT angiogram revealed a broncho-pulmonary arterial fistula, a rare cause of haemoptysis in children. Endovascular embolisation resulted in short-term symptom resolution; however, haemoptysis recurred months later, leading to re-embolisation. This case highlights a stepwise approach to the workup of large volume haemoptysis.

Background

Haemoptysis, the expectoration of blood from the respiratory tract, is a rare symptom in children. While most cases are self-limiting, mortality rates can exceed 50% when massive and untreated.¹ Death is typically due to asphyxiation rather than exsanguination,² highlighting the need for immediate recognition. Lower respiratory tract infection accounts for approximately 40% of cases.³ Other causes of pulmonary haemorrhage are listed in table 1.⁴

Table 1.

Aetiology of pulmonary haemorrhage

Localised pulmonary haemorrhage	Diffuse pulmonary haemorrhage
Bronchiectasis, infection	Immune—granulomatosis with polyangiitis, microscopic polyangiitis, idiopathic pulmonary capillaritis, anti-GBM disease, systemic lupus erythematosus, Henoch Schonlein purpura, Behcet’s syndrome
Foreign body aspiration
Vascular malformations—pulmonary arteriovenous malformation, vascular fistula, aneurysmal-type vessels (dieulafoy lesion)
Congenital anomalies—sequestration, bronchogenic cyst	Idiopathic pulmonary haemosiderosis
	Coagulation disorders
	Post-bone marrow transplantation
Trauma	Acute idiopathic haemorrhage of infancy
	Cardiovascular causes—congenital heart disease, pulmonary hypertension, pulmonary veno-occlusive disease, mitral stenosis
Tumour
Iatrogenic	Toxic—cocaine, azathioprine, penicillamine, propylthiouracil

Adapted from Nugent et al.⁴

Anti-GBM, Anti-glomerular basement membrane.

Several systems for classifying haemoptysis as ‘massive’ have been proposed,^{3 5 6} such as more than 240 mL in cystic fibrosis patients,⁷ or >8 mL/kg (up to 600 mL) in the general population.³ Immediate recognition of such cases is crucial as respiratory distress can progress rapidly in children with ongoing pulmonary haemorrhage. A thoughtful, sequential approach is vital and may involve multidisciplinary services including but not limited to paediatrics, respirology, otolaryngology, rheumatology, infectious diseases, interventional radiology, anaesthesiology, surgery, and intensive care. This case highlights this clinical approach.

Case presentation

A 9-year-old previously healthy girl presented with sudden onset haemoptysis, >300 mL over 2 hours (figure 1). The child initially described vomiting bright red blood therefore intravenous pantoprazole was started for potential gastrointestinal (GI) bleeding. She was transferred from her community hospital to a tertiary paediatric centre. Her haemoglobin dropped from 130 g/L to 115 g/L over 7 hours.

Figure 1.

Basins having collected expectorated blood and clots while in hospital on first presentation of haemoptysis.

There were no preceding infectious symptoms such as rhinorrhoea, cough or fever, nor was there chest pain or dyspnoea. She had recently returned from a trip to Mexico without incident. There was no family history of lung disease, congenital anomalies or bleeding diathesis, and no personal history of bleeding, previous haemoptysis, trauma, drug or toxin exposure, and no concern for retained foreign body.

On examination she was in no distress and appeared well with normal vital signs including an oxygenation saturation of 98% in room air and a respiratory rate of 20. There was minimal right sided decreased air entry without adventitious sounds. Remainder of the examination was unremarkable.

Abdominal ultrasound was completed to examine for liver disease in the context of potential haematemesis. An echogenic focus in the right lower lobe was found incidentally and right lower lobe consolidation confirmed on chest X-ray. She was started on intravenous ampicillin therapy for pneumonia. Intravenous pantoprazole was discontinued when it became clear that episodes were preceded by coughing. Despite addition of ceftriaxone, haemoptysis continued and her haemoglobin dropped from 115 g/L to 103 g/L within 48 hours of transfer to the tertiary care hospital.

Investigations

Bloodwork showed normal white cell and platelet counts. Haemoglobin was 130 g/L on initial presentation, but dropped to 115 g/L and then 103 g/L within 72 hours. There was no eosinophilia.

The following were all normal: IgG, IgA, IgM, C3, C4, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), international normalized ratio (INR), partial thromboplastin time (PTT), fibronogen level, von Willebrand factor (vWF), and vWF activity.

Expectorated sputum culture grew usual flora. Throat swab was negative for atypical bacteria by PCR.

X-rays taken over several days showed worsening right lower and middle lobe consolidation with mediastinal shift despite intravenous antibiotics (figure 2).

Figure 2.

Chest X-ray while awaiting bronchoscopy on first presentation depicting right lower lobe and right middle lobe opacification with associated rightward mediastinal shift, likely atelectasis.

First chest CT with contrast revealed a well circumscribed 0.8 cm×1.2 cm soft tissue density within the right mainstem bronchus (RMB) distal to the carina (figure 3). There was associated plugging of the RMB with segmental collapse of the right middle lobe, and near complete collapse of the right lower lobe. Scattered ground glass opacities were seen within the left lung base and sections of the right upper and middle lobes. Significant mediastinal shift rightwards was present, with no pleural, bone, or cardiac abnormalities or lymphadenopathy. Pulmonary arterial tree appeared grossly normal.

Figure 3.

CT chest revealing the well circumscribed 0.8 cm × 1.2 cm soft tissue density (yellow arrow) within the right mainstem bronchus distal to the carina.

Pulmonary angiogram was performed to examine the pulmonary arterial circulation for vascular abnormalities; none were detected.

Bronchoscopy revealed a clot extending from the right lower lobe lateral segment to the RMB that was removed via rigid bronchoscopy (figure 4). Flexible bronchoscopy distal to the clot site revealed no active bleeding, and no pulsatile or otherwise irregular lesion. No foreign body was discovered and pathological examination demonstrated only mucus, haemorrhage, and fibrinous material. Samples from bronchoalvolear lavage were negative for bacteria, virus, and fungus.

Figure 4.

Images from joint rigid and flexible bronchoscopy, depicting extensive clot to the right mainstem bronchus, evacuated using forceps via rigid bronschopy.

Repeat chest CT angiogram then revealed an area of possible irregularity of the distal vessels in the right lateral basal segment.

Pulmonary angiography was repeated, this time examining the bronchial arterial circulation. This examination revealed a bronchial artery to pulmonary artery (BA-PA) fistula between a peripheral branch of the right bronchial artery and a peripheral right pulmonary arterial branch within the right lung base (figure 5).

Figure 5.

Right bronchial arteriogram before embolisation showing the arterio-arterial fistula (white arrowhead) in the right lower lobe between the two branches of the right bronchial artery (white arrows) and a small peripheral branch of the right lower lobe pulmonary artery (black arrows). Contrast fills a second branch of the right lower lobe pulmonary artery because of the communication between branches of the pulmonary arteries.

Differential diagnosis

Initially an infection was suspected based on consolidation visualised on X-ray. However, the lack of infectious symptoms, a negative sputum culture, and lack of improvement with antibiotic therapy made a bacterial cause unlikely. Viral studies were negative. A fungal infection or tuberculosis (TB) was considered given the initial appearance of an endobronchial lesion; however, airway samples were negative for fungus and TB. Cystic fibrosis can present with haemoptysis; however, there was no history of pulmonary infections or malnourishment, and no bronchiectasis on CT.

There was no history of foreign body, and the patient was developmentally normal with no history of choking or aspiration. There was no history of trauma to explain this presentation.

There was no family history or personal history of significant epistaxis or physical examination findings to suggest hereditary haemorrhagic telangiectasia.

No evidence of cardiac or lung congenital abnormalities such as sequestration were visualised on CT.

There were no systemic rheumatological symptoms and she had a normal urinalysis, ESR, and CRP making vasculitis unlikely. A negative antineutrophil cytoplasmic autoantibody (ANCA) result was obtained during her second presentation.

She lacked risk factors for pulmonary embolism (PE) such as use of the contraceptive pill or recent surgery. PE was not visualised on any imaging.

The initial CT was suggestive of a soft tissue density in the RMB consistent with a tumour such as a carcinoid tumour. A dieulafoy lesion (large tortuous arteriole) was also suspected. Neither of these rare lesions was visualised on bronchoscopy.

Haematemesis, or haemoptysis secondary to aspirated blood from the GI tract, was considered on admission. However, the patient repeatedly coughed just prior to blood expectoration making primary haemoptysis far more likely. Abdominal ultrasound was normal, reducing suspicion for a GI bleed. Upper GI endoscopy was considered, but held when chest CT angiogram revealed an anomaly.

Pulmonary angiogram of the bronchial system was ultimately required to make the diagnosis of a vascular malformation. Given the proximity of the identified lesion to the haemorrhage and having ruled out other common causes of pulmonary haemorrhage, this vascular malformation was deemed as the underlying cause.

Treatment

Treatment for this patient was performed by interventional radiology at a tertiary care hospital and involved fistula embolisation using polyvinyl alcohol (PVA) material immediately after detection via pulmonary angiography (figure 6).

Figure 6.

Right bronchial arteriogram after embolisation showing occlusion distally of the two branches of the right bronchial artery and complete closure of the vascular fistula.

Outcome and follow-up

No further haemoptysis occurred post-embolisation while in hospital or immediately post-discharge. After 1 month haemoptysis free, activity restriction was lifted.

Three months following her initial presentation her forced expiratory volume in 1 s (FEV1) was 129% of predicted with a negative bronchodilator response. Forced vital capacity was 134% of predicted. Total lung capacity was 129% of predicted with no evidence of gas trapping. Chest X-ray was unremarkable. Diffusion capacity was normal. She was asymptomatic with no further haemoptysis.

At 6 ½ months post-discharge, she presented again with moderate haemoptysis of 120 mL. There was no history suggestive of trauma or infection. Repeat investigations for vasculitis including ANCA and urinalysis were negative. Chest CT angiogram revealed opacification of the right middle and lower lobes with patchy ground glass opacities bilaterally. The right lower lobe bronchus was again occluded by an apparent soft-tissue density, concerning for recurrent blood clot. Angiogram demonstrated an arterio-arterial fistula within the right lower lobe, suspected to be a recanalisation of the original fistula, which was then successfully embolised with diluted glue. Given the risk of re-bleeding in light of her representation, angiogram was repeated to confirm no residual connection.

Six months following second embolisation, pulmonary function and chest X-ray remained normal. She was able to return to physical activities without restriction or symptoms, and has had no further episodes of bleeding 1 year following her initial presentation.

Discussion

Early recognition with prompt and sequential workup was crucial in this case. Given that asphyxiation is the leading cause of death in massive haemoptysis,² searching for an underlying diagnosis prior to discharge is of paramount importance. In our case, the diagnosis of BA-PA fistula was achieved by angiography, preceded by early CT imaging and both rigid and flexible bronchoscopy.

Reports of massive childhood haemoptysis secondary to vascular anomalies have been reported over the past two decades, although largely due to arteriovenous malformations (AVMs).^8–11 Aberrant arteries—either supplying normal lung segments or in fistulisation with the pulmonary arterial system—are rarer. There are two vascular systems present in the lung, bronchial (arising from systemic circulation) and pulmonary. Aberrant arteries can arise from either. Abdulhamid and Forbes described five cases of massive haemoptysis resulting from dilated aberrant arteries, all of which arose from the systemic arterial supply¹²; BA to pulmonary artery fistulae are rarer. Nugent et al describe a similar case to ours: a BA-PA fistula successfully embolised with PVA.⁴

Some of the cases described above were compiled in The Clinical Respiratory Journal in 2016. The series included five cases of systemic arterial malformations, two cases of AVM supplied by BA, three cases of BA malformations alone, and one case of bronchopulmonary arterial anastomosis (which was present in our patient).¹³ This makes our case the third reported paediatric case of BA-PA fistula (including Nugent et al). BA-PA fistula is an exceedingly rare entity in children, so it is difficult to determine underlying aetiologies. However, they do appear to be most likely sporadic or congenital in nature.^{13 14}

In the series, BA embolisation (BAE) was performed for those involving BA supply (n=6); all were successful. However, follow-up in these BA cases was reported in only three of the six cases from 18 to 42 months post-embolisation. One case recurred with massive pulmonary haemorrhage at 14 months post-embolisation, and required re-embolisation using NBCA (N-butyl-cyanoacrylate), a liquid embolisation agent.¹³ At 42 months follow-up, this patient was well without a third recurrence. The true rates of recurrence and factors affecting recurrence remain unknown given the paucity of cases. Nevertheless, given that two out of four BA cases reporting follow-up (our case included) describe recurrence with massive pulmonary haemorrhage, we suggest ongoing follow-up to ensure complete resolution post-embolisation.

Much of our understanding of outcomes following BAE for haemoptysis comes from adult data. Sopko and Smith described BA angiography with embolisation as a mainstay in the treatment of haemoptysis, with major complications being rare and immediate success rates ranging from 85% to 100%.¹⁵ Recurrence rates for arterial anomalies are quoted at 10%–55% in adults.¹⁵

Clinical management considerations for haemoptysis in children largely stem from cystic fibrosis guidelines. If haemodynamically stable, haemoptysis workup is suggested, which may include the following on a case-by-case basis: (1) laboratory testing (including but not limited to complete blood count (CBC), bleeding dyscrasia workup, and urinalysis for haematuria), (2) imaging (including X-ray, CT with contrast), and (3) intervention including flexible or rigid bronchoscopy.⁷ Then, one should optimise treatment for underlying disease. Should bleeding continue or recur: consider further bronchoscopy, CT, and/or BAE—although proceeding directly to BAE is recommended in cystic fibrosis with massive haemoptysis. Surgical resection may be warranted if embolisation and/or other treatments are unsuccessful and there is proven bleeding from a focal source.⁷

Our case brings to light clinical management considerations for haemoptysis, First, if no clear cause is found, imaging the arterial supply, including both the bronchial and pulmonary vascular beds, is important especially in the setting of massive haemoptysis. While tracheal varices (tracheal venous congestion) has been reported as a cause of pulmonary haemorrhage,¹⁶ massive haemoptysis is most likely to occur from an arterial source.³ Second, in the case of a stable patient, CT chest can help guide bronchoscopy. We added tumour or aneurysmal defect such as a dieulafoy lesion to our differential in light of findings on high resolution imaging (figure 3). This area was targeted via bronchoscopy, and found to be blood clot. In such cases, we suggest rigid bronchoscopy with flexible bronchoscopy to achieve optimal clot evacuation and visualisation of distal airways, respectively, rather than expectant management for clot evacuation. Third, clinical follow-up post-embolisation procedure is important since recanalisation of fistula with recurrent haemoptysis is not uncommon.^{12 13} This follow-up should include chest X-ray and pulmonary function testing (examining for obstruction, or increased diffusing capacity for carbon monoxide (DLCO) due to haemorrhage). Our case suggests that relatively early recurrence is possible, even after immediate success post-BAE. Additionally, Sismanlar’s paediatric case of a BA-PA fistula rebleeding at 14 months post-intervention suggests that long term follow-up beyond 1 year is also prudent.

Patient’s perspective.

One day I coughed blood, and it was the scariest day of my life. When I arrived at the hospital, I was very nervous and no one knew what I had. In total, I had six different teams visit and every suspicion they had was not turning up anything. Being poked and prodded was the worst experience.

Countless needles in the pursuit of what was causing the bleeding was a daily, even hourly fear. While the time was as enjoyable as a 20-day hospital stay could be (minus the needles), it was nowhere near as fun as being home with my family and friends including my hockey team.

Six months later at a hockey tournament, the bloody cough started again. I was worried, not because it hurt in any way, but more so because I knew the needles were coming back; and that rather than playing hockey with my team and enjoying a tournament and all the fun that comes with it, I would be in hospital again getting poked with needles.

It has been well over 9 months now with no repeat, and not a day goes by where my family and I do not think about my health! I do follow-ups with the amazing staff, and my family and I are confident that the next time around, they will be able to fix the issue once and for all.

Learning points.

• Massive haemoptysis, especially in the setting of a drop in haemoglobin, warrants immediate transfer to a facility that has the capacity for diagnostic and therapeutic intervention including: bronchoscopy, vascular embolisation, and surgery.

• Bronchial to pulmonary artery fistula is rare, although it should be suspected if initial workup for infection, bronchiectasis, congenital, immune, rheumatological, and cardiovascular causes are unremarkable.

• While CT chest and CT-angiogram are useful modalities in identifying causes of massive haemoptysis, rigid and flexible bronchoscopy in addition to interventional angiography are often required to diagnose and manage bronchial artery anomalies.

• In the setting of airway obstruction due to clotted material a proactive approach should be considered via bronchoscopy for haemorrhage/clot clearance from the airway.

• Adequate long-term follow-up is suggested in light of this case and others published on paediatric haemoptysis recurrence. This includes lower threshold to undergo repeat pulmonary angiography in cases of recurrence.