Revista Americana de Medicina Respiratoria - Volumen 15, Número 2 - Junio 2015

Artículos Originales

Twenty-Year Experience in Lung Transplantation: Complications of the Airways. The Role of Multidetector Computed Tomography

Autor : Matías R. Mazzucco1, Juan M. Osses2, Rosalía Ahumada2, Graciela Wagner2, Jorge Cáneva2, Franco Marinucci1, Adriana Martínez1, Roberto Favaloro2, Alejandro Bertolotti2

1Diagnostic Imaging Service, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina 2Intrathoracic Transplantation Division, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina

 

Abstract

Introduction: The complications of airways in lung transplant recipients are an important cause of morbidity and mortality, reaching up to 18% of patients according to various reports. Dehiscence, stenosis and malacia are included.
Objective: Describe our experience in patients with complications of airways after lung transplantation.
Secondary Objective: Demonstrate the usefulness of multidetector computed tomography for the diagnosis, treatment and monitoring of airways complications in lungs transplanted patients.
Materials and Methods: The medical records of lungs transplanted patients with bronchographic diagnosis of the airways complications were reviewed and analyzed. Furthermore CT findings of these patients were compared with the bronchoscopy diagnosis to determine their utility.
Results: Among 325 lung transplants performed in 20 years, 65 (20%) showed airways complications. The most frequently reported complications were stenosis in 51 patients (78.5%), malacia (15%) and dehiscence (13.5%).
All patients with stenosis or malacia received first a therapeutic endoscopic dilatation; 33 of them had re-stenosis and in 30 patients a stent was implanted.
Dehiscences were treated with surgical intervention, stenting or closing with Histoacryl.
In 30 patients with clinical suspicion of significant airways complications, MDCT proved to be diagnostic in 100% of cases.
Conclusion: The airways complications should always be suspected in cases of dyspnea, fever or worsening functional class associated with spirometry forced expiratory volume decline in one second.
Also, MDCT with multiplanar and 3D reconstructions showed high accuracy for diagnosis, therapy planning and subsequent control.

Key words: Lung transplant; Airways complications; Bronchial stenosis; Malacia; Bronchial dehiscence.


 

Introduction

Lung transplantation is today a treatment option that allows for a survival increase in several end-stage pulmonary diseases including, but not limited to, cystic fibrosis, emphysema, idiopathic pulmonary fibrosis and idiopathic pulmonary hypertension1-3.
At present, this surgical procedure is associated with a survival benefit of 75%, 50%, 25%, and 15% at 1, 5, 10, and 15 years, respectively4. This fact is influenced by an improvement in immunosuppressive therapy, surgical techniques and greater knowledge of the complications2, 4.
Since the first lung transplantation performed in 1963 up to this day, ACs are an important cause of morbidity and mortality in these patients.2, 5. Presently, they show an incidence of up to 18% according to different reports, with an associated mortality of 2-4%5, 6.
ACs in lung transplant patients include early onset complications such as necrosis with dehiscence, which appear during the first 3 months after surgery, and late onset complications, stenosis and malacia, which generally appear after the 3-month period post-transplantation4, 7.
The diagnosis of these ethiologies is usually performed through FB; however, the MDCT with multiplanar reconstructions and 3D sequences of virtual endoscopy is a non-invasive option capable of showing these alterations of the airways1, 3, 8.
The purpose of this study is to show our experience with this kind of disease, as well as the tomographic signs of ACs and the way multiplanar or 3D reconstructions contribute to their diagnosis.

Objective

Demonstrate our experience in patients with ACs who have undergone lung transplantation.
Secondary Objective: Demonstrate the usefulness of MDCT for the diagnosis and post-treatment monitoring of ACs in lung transplant patients.

Materials and Methods

All the medical records of patients with AC diagnosis obtained via FB have been reviewed and analyzed.
Also, tomographic findings of 30 patients with significant clinical suspicion of ACs were compared to FB findings. Our suspicion was established based on clinical symptoms such as dyspnea, fever, chills or functional class worsening associated with FEV1.
35 out of 65 patients with ACs were excluded from this evaluation because of missing tomographic studies.
All of these patients received certain type of treatment, such as endoscopic dilatation, laser treatment or bronchial stenting, depending on the kind of complication. Also, the usefulness of tomography for post-treatment monitoring has been assessed.

Results

Certain kind of airway complication has been identified in 65 out of 325 transplants performed since 1994 up to this day, representing a 20% prevalence. The male/female ratio was 1.7 (41 males, 24 females), the age range was from 15 to 66 years, with a mean age of 44.5 years.
Baseline diseases that motivated the transplants were emphysema (cases with a BODE index between 7 and 10 or FEV 1 and DLCO < 20% of predicted value with homogeneous involvement), cystic fibrosis and idiopathic pulmonary fibrosis, among other diseases (Table 1). 31 and 34 patients received double-lung and single-lung transplants, respectively.
The most frequently reported complication among the patients included in the study was bronchial stenosis in 51 patients (78.5%), being the bronchus intermedius the most affected segment (Drawing 1). Way below that percentage within the range of complications were malacia and dehiscences, in 10 (15%) and 9 (13.5%) patients, respectively.

Table 1. Disease that motivated transplantation in patients with ACs
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Drawing 1. Bronchial Stenosis distribution according to its anatomical impact.

Out of 10 patients with diagnosis of malacia, there were 5 cases of primary left bronchus involvement and 2 of primary right bronchus involvement, 2 cases of primary right bronchus involvement in association with the bronchus intermedius and 2 cases of involvement of both primary bronchi.
In the case of dehiscence, 5 patients showed right-sided complication and 4 patients showed left-sided complication.
Mean time from onset was 6.6 months for bronchial stenosis, 6 months for malacia and 4.5 weeks for dehiscence (Drawings 2, 3, 4).

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Drawing 2. Time from onset of stenosis in various evaluated patients.

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Drawing 3. Time from onset of bronchomalacia in various evaluated patients.

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Drawing 4. Time from onset of dehiscence in various evaluated patients.

(Figures 1, 2): the other 3 patients received laser treatment, 1 of which showed restenosis (primary left bronchus) and subsequently underwent stent implantation, too.

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Figure 1. 57-year-old patient who underwent right lung transplantation due to idiopathic pulmonary fibrosis and diagnosis of stenosis of bronchus intermedius. (a, b) Virtual and endoscopic bronchoscopy showing severe stenosis of bronchus intermedius. (c) Endoscopic bronchoopy after placement of self-expandable stent in the right main-stem bronchus.

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Figure 2. Spirometric values before (a) and after (b) placement of self-expandable stent of previous patient. Note the immediate improvement of FEV1 percentage, from 32 to 51%.

Only 4 of the patients with endobronchial stents showed restenosis at the stent level or distal to the stent; they were treated with endoscopic dilatation. Two patients (3%) died from an infection associated with multiple organ failure.
All patients with dehiscence were treated with surgical correction, stenting or dehiscence closure with Histoacryl.
Computed Tomography in Lung Transplantation Patients with significant clinical suspicion of airway complication (30 patients) underwent a MDCT that proved to be diagnostic in 100% of the cases. Through the MDCT it was possible to observe caliper reduction of stenotic bronchi, bronchial failure in patients with malacia during expiration and direct and indirect signs of dehiscence. Furthermore, the MDCT was useful for post-treatment monitoring, showing the presence of restenosis or new dehiscence signs (Figure 3).

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Figure 3. 57-year-old patient who underwent right lung transplantation due to idiopathic pulmonary fibrosis and diagnosis of stenosis of right main-stem bronchus and bronchus intermedius. (a) Coronal MinIP reconstructions showing severe stenosis (white arrow) and (b) following self-expandable stent placement extending from main-stem bronchus to bronchus intermedius (black arrow). (c, d) Oblique multiplanar reconstructions aligned towards the bronchus before and after placement of self-expandable stent, respectively.

Discussion

At present, transplantation is the best treatment option for end-stage pulmonary diseases, allowing the patients to prolong and improve their quality of life2, 3.
Usually, the bronchi receive double arterial blood supply by the branches of the pulmonary artery and by the bronchial arteries, which arise from the intercostal arteries or directly from the descending aorta. The bronchial arteries are inevitably cut when performing the ablation. Thus, arterial blood to the bronchi is supplied by backflow from the distal branches of the pulmonary artery towards the bronchial arteries, through collaterals between the two streams, which can take up to 4 weeks to develop. So, postoperative bronchial ischemia plays a major role in the appearance of ACs. Broncial ischemia is worsened by factors which increase pulmonary vascular resistance or reduce the blood flow. These factors include poor graft preservation, reperfusion injury, acute rejection, infections and the use of prolonged positive pressure ventilation1, 6, 9.
Dehiscence of bronchial anastomosis occurs normally within the first month after surgery. Dehiscences may be suspected via tomography when there is extraluminal air adjacent to the anastomosis, which may be associated with the presence of a defect or irregularity at the bronchial wall. The presence of neumothorax or pneumomediastinum ipsilateral to the anastomosis is an indirect sign of bronchial dehiscence (Figure 4). We should consider that the presence of extraluminal air at the pleura or mediastinum may be seen 2 or 3 weeks (generally no more than 4 weeks) after surgery, so it should be considered as a sign of dehiscence when detected too late or if there is a new image of air in these areas.
Computerized axial tomography may be insufficient for the evaluation of dehiscences of bronchial anastomoses. In these cases, multiplanar reconstructions or Minimum Intensity Projections (MinIP) increase the range of diagnostic possibilities3, 4.

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Figure 4. 62-year-old patient who underwent right lung transplantation due to emphysema and diagnosis of dehiscence of main-stem bronchus. Thorax computed tomography: (a, b) axial slices and (c) coronal slice showing direct signs of dehiscence, such as the presence of extraluminal air at the bronchus (black arrows), as well as indirect signs of dehiscence, including pneumomediastinum and right anterior pneumothorax (white arrows), respectively.

Airway stenosis generally occurs 4 weeks after transplantation and may affect the anastomosis site or extend distally from it. Less than or equal to 50% stenosis is classified as Grade I, and greater than 50% stenosis is classified as Grade II3, 4 (Figure 5).

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Figure 5. 32-year-old patient who underwent double-lung transplantation due to pulmonary hypertension. (a) Coronal slices with MinIP reconstruction showing stenosis of right main-stem bronchus (white arrow). (b) 3D reconstruction of the airway also showing stenosis (black arrow).

The diagnosis is generally made via FB; however, this method is invasive, requires sedation and may not be tolerated by patients with decreased pulmonary function. In addition, in cases of severe stenosis, the bronchoscope is not able to go through it or to provide extraluminal information of the parenchyma that is essential for correct treatment planning. Thus, MDCT with multiplanar reconstructions, 3D images or virtual endoscopy becomes truly important as it provides exact information of the stenosis grade and extension, which is useful to establish the treatment3, 8.
Bronchomalacia is defined as 50% upper airway obstruction after expiration, and appears lately after transplantation. The bronchoscopy provides effectiveness, once the respiratory failure of the affected bronchus has been shown; however, this complication can be difficult to evaluate, depending on the clinical status of the patient. Double protocol with computed tomography slices at inspiration and expiration is capable of showing 50% upper bronchus failure and the extension of this complication3, 10 (Figure 6).

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Figure 6. 56-year-old patient who underwent right lung transplantation due to idiopathic pulmonary fibrosis and diagnosis of malacia of bronchus intermedius. MinIP coronal reconstructions at (a) inspiration and (b) expiration showing 50% upper bronchus intermedius failure, in agreement with the diagnosis of bronchomalacia.

Treatment of different ACs may include laser debridement, endoscopic dilatation, stenting or, in some cases, surgery1, 6.
Small dehiscences may be corrected without sequelae. In partial dehiscences, bronchial stenting is the treatment of choice. Since this complication may be mortal, surgical resolution shall always be considered by the surgical team2, 10.
Laser debridement or endoscopic dilatation are primary procedures in the treatment of bronchial stenosis11, 12. Patients often show restenosis after these procedures, in which case stent implant via endoscopy is indicated10. In cases of symptomatic bronchomalacia, the first line treatment is the placement of a rigid metallic endobronchial stent to avoid bronchus failure1, 10.
Finally, the MDCT also showed usefulness for subsequent monitoring of these treatments (Figure 7). It also allows for the evaluation of complications, including restenosis, stent migration and fracture as the most frequent ones, establishing the bronchial diameter, the migration site and the status of the stent, respectively1, 6, 10 (Figure 8).

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Figure 7. 29-year-old patient who underwent double-lung transplantation 14 years ago due to cystic fibrosis and with diagnosis of stenosis of left main-stem bronchus treated with laser. Thorax computed tomography: (a) axial slice and (b) coronal slice with MinIP reconstruction showing little residual stenosis 14 years post-treatment (black arrows).

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Figure 8. 41-year-old patient who underwent double-lung transplantation due to pulmonary hypertension with stenosis and stent placement in both main-stem bronchi. (a, b) Computed tomography coronal and axial slices showing both intra-stent restenosis and restenosis distal to the stent at the right main-stem bronchus.

Conclusion

On the basis of our experience and in accordance with the references, we can say that ACs are an important cause of morbidity and mortality in lung transplant patients. Thus, this disease should always be suspected in patients with such background, especially within the first few months after surgery, upon the appearance of signs and symptoms suggestive of this disease, namely dyspnea, fever and functional class worsening associated with FEV1.
It is also important to mention the high degree of effectiveness provided by MDCT and multiplanar or 3D reconstructions for diagnosis, treatment planning and subsequent monitoring of the disease.

Conflicts of Interest: The authors declare there is no conflict of interest related to this publication.

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Mujer joven con afectación pulmonar bilateral y alteración de la conciencia

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