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Treatment of postoperative tracheal granulation tissue with inhaled budesonide in congenital tracheal stenosis
Journal of Pediatric Surgery 49 (2014) 293–295
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Treatment of postoperative tracheal granulation tissue with inhaled budesonide in congenital tracheal stenosis Akiko Yokoi a,⁎, Makoto Nakao a, Yuko Bitoh a, Hiroshi Arai a, Yoshihiro Oshima b, Eiji Nishijima a a b
Department of Pediatric Surgery, Kobe Children’s Hospital, Kobe, Japan Department of Cardiovascular Surgery, Kobe Children’s Hospital, Kobe, Japan
a r t i c l e
i n f o
Article history: Received 1 November 2013 Accepted 10 November 2013 Key words: Congenital tracheal stenosis Tracheoplasty Tissue granulation Inhaled corticosteroids
a b s t r a c t Purpose: Tracheal obstruction by granulation tissue can compromise the postoperative course in congenital tracheal stenosis (CTS). Balloon dilatation and stenting may be required. Budesonide is a corticosteroid with topical anti-inflammatory effects. In 2008, we used inhaled budesonide for treatment of postoperative granulation tissue for the first time in CTS, resulting in significant improvement. The aim of this study was to evaluate the efficacy of inhaled budesonide for treatment of postoperative granulation tissue in CTS. Methods: Retrospective chart review was conducted. From 2004 through 2011, we performed 39 tracheoplasties. Forced stenting ± balloon dilatation (S/B) was required when airway obstruction with tissue granulation was life-threatening. We compared the requirement for S/B between the early group without budesonide (2004–Nov. 2008, Early) and the late group with budesonide (Dec. 2008–2011, Late). Statistical analysis was performed using Fisher’s Exact test. Results: Eleven of 22 in Early and 8 of 17 in Late were successfully extubated, never having had lifethreatening tissue granulation. The remaining patients in each group (11 in Early and 9 in Late) required tracheostomies due to postoperative complication. Ten in Early and 5 in Late with tracheostomies developed granulation tissue. Of these patients, the 10 in Early required S/B, while none of the 5 in Late required S/B (P = .0003). Bronchoscopy demonstrated significant regression of granulation tissue in all cases treated with inhaled budesonide. Conclusion: Inhaled budesonide is effective for treatment of tracheal granulation tissue in patients with tracheostomies after repair of CTS. © 2014 Elsevier Inc. All rights reserved.
Congenital tracheal stenosis (CTS) is a relatively rare condition with high mortality rate. Slide tracheoplasty is the procedure of choice, especially for long segment of congenital tracheal stenosis [1]. Postoperative complications include bronchotracheal malacia, recurrent stenosis, and intraluminal tissue granulation [2–4]. These complications can cause life-threatening airway obstruction. The treatment of tissue granulation requires balloon dilatation and stenting [5,6]. Balloon dilatation causes tracheal wall disruption, resulting in a need for long-term stenting [7]. Intraluminal stenting also causes tube-tip granulation, again requiring balloon dilatation or laser ablation and deeper stenting. Inhaled budesonide is a corticosteroid with topical anti-inflammatory effect widely used as first-line therapy for asthma [8]. In 2008, we used inhaled budesonide for treatment of postoperative granulation for the first time in congenital tracheal stenosis, resulting in a significant improvement. Since then, we have routinely used inhaled budesonide for the treatment of tracheal granulation tissue. The aim
⁎ Corresponding author at: Kobe Children’s Hospital, Department of Pediatric Surgery, 1-1-1 Takakuradai, Sumaku, Kobe Japan. Tel.: +81 78 732 6961; fax: +81 78 735 0910. E-mail address: [email protected] (A. Yokoi). 0022-3468/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpedsurg.2013.11.041
of this study was to determine the efficacy of this treatment in preventing a significant cause of postoperative airway obstruction in congenital tracheal stenosis.
1. Materials and methods With the approval of the Kobe Children’s Hospital institutional review board (No.R25-1), retrospective chart reviews were conducted for surgically managed CTS in the period Jan. 2004 through Dec. 2011. A variety of surgical procedures were performed; these included tracheoplasties (standard posterior-anterior slide tracheoplasties and modified right-left slide tracheoplasties) and resection and end-toend anastomosis. Forced stenting ± balloon dilatation was performed when airway obstruction with tissue granulation was life-threatening. From December 2008, budesonide inhalation suspension (Pulmicort Respules®, AstraZeneca) 0.25 mg twice daily was used as the treatment of first choice for the management of tissue granulation after tracheoplasty. We compared the requirement for stenting, with or without balloon dilatation, between the Early group not receiving budesonide (from 2004 to November 2008) and the Late group with budesonide (December 2008 through 2011). Statistical analysis was
294
A. Yokoi et al. / Journal of Pediatric Surgery 49 (2014) 293–295
Table 1 Series of children with congenital tracheal stenosis (2004–2011).
Total Postoperative tracheostomy Tissue granulation Requiring stent with or without balloon dilatation
Early group (n)
Late group (n)
P value
22 11 10 10
17 9 5 0
1.00 0.13 b.0001
performed using Fisher’s exact test. Bronchoscopy was also performed before and after treatment with inhaled budesonide. 2. Results From Jan. 2004 through Dec. 2011, we performed 39 tracheoplasties (standard posterior-anterior slide tracheoplasties n = 30; modified right-left slide tracheoplasties n = 3; and resection and end-to-end anastomosis n = 6) for CTS. Eleven of 22 (50%) children in the Early group and 8 of 17 (47.1%) patients in the Late group were successfully extubated, never having had life-threatening tissue granulation. The other 11 and 9 children in each group required tracheostomies, due to postoperative bronchotracheal malacia or recurrent stenosis after tracheoplasty (P = 1.00). Ten out of 11 patients and 5 out of 9 patients in each group had intraluminal tissue granulation (P = 0.13). Stenting with or without balloon dilatation was required in 10 patients in the Early group, while none required stenting in the Late group (P b .0001) (Table 1). Bronchoscopy showed significant improvement with inhaled budesonide in the Late group (Fig. 1).
To address this, we initially used systemic or intratracheal steroids in an effort to regress intraluminal granulation. However, the observed efficacy of systemic steroids was limited, and long-term administration caused significant morbidity, such as bony fractures and infections. We subsequently used inhaled budesonide as first line therapy for tracheal tissue granulation after we observed the remarkable efficacy of this treatment in the first case in 2008. In all cases subsequent to 2008, tissue granulation regressed significantly in several days, avoiding forced stenting with balloon dilatation. Topical budesonide has been reported as an effective treatment for nasal polyps [9] and inflammatory bowel disease [10,11], with the advantage of effective local activity, minimized systemic toxicity, and limited adverse effects [12,13]. Roh et al. [14] reported the efficacy of inhaled budesonide in the treatment of intubation granulomas. Those reports suggested to us that budesonide could be an effective therapy for tissue granulation after tracheal reconstruction in patients with congenital airway stenosis. The Airway Reconstruction Team at the Hospital for Sick Children, Toronto [15] reported that tracheoplasty patients routinely received 24 hours of postoperative intravenous dexamethasone and inhaled budesonide, and “surprisingly” none developed intraluminal granulations, supporting the efficacy of budesonide for preventing tracheal granulation tissue. Inhaled budesonide could be used as prophylaxis of tracheal granulation in the patients who have postoperative tracheostomy. In conclusion, our experience suggests that inhaled budesonide can be effective for the treatment of tracheal granulation tissue, and may therefore provide an important option in the management of congenital tracheal stenosis.
References 3. Discussion Our study shows the efficacy of inhaled budesonide for the treatment of postoperative tracheal tissue granulation in CTS. Postoperative bronchotracheal malacia and recurrent stenosis may significantly compromise the tracheal lumen and thus patient safety, requiring long-term stenting. Tracheal granulation tissue, usually arising at the tip of the stenting tube, causes life-threatening airway obstruction, which is associated with high mortality rate in congenital tracheal stenosis. We had been treating intraluminal tissue granulation by inserting a stent deeper to bypass the granulation, with or without balloon dilatation, which in turn resulted in repeated and intractable deeper tube-tip granulation.
[1] Rutter MJ, Cotton RT, Azizkhan RG, et al. Slide tracheoplasty for the management of complete tracheal rings. J Pediatr Surg 2003;38:928–34. [2] Lang FJ, Hurni M, Monnier P. Long-segment congenital tracheal stenosis: treatment by slide-tracheoplasty. J Pediatr Surg 1999;34:1216–22. [3] Tsugawa C, Nishijima E, Muraji T, et al. Tracheoplasty for long segment congenital tracheal stenosis: analysis of 29 patients over two decades. J Pediatr Surg 2003;38: 1703–6. [4] Koopman JP, Bogers AJ, Witsenburg M, et al. Slide tracheoplasty for congenital tracheal stenosis. J Pediatr Surg 2004;39:19–23. [5] Elliott M, Hartley BE, Wallis C, et al. Slide tracheoplasty. Curr Opin Otolaryngol Head Neck Surg 2008;16:75–82. [6] Manning PB, Rutter MJ, Border WL. Slide tracheoplasty in infants and children: risk factors for prolonged postoperative ventilatory support. Ann Thorac Surg 2008;85:1187–91 [discussion 1191–1192]. [7] Wright CD. Treatment of congenital tracheal stenosis. Semin Thorac Cardiovasc Surg 2009;21:274–7.
Fig. 1. Child developing postoperative tissue granulation in the late group. Bronchoscopic findings before (A) and after (B) treatment with inhaled budesonide.
A. Yokoi et al. / Journal of Pediatric Surgery 49 (2014) 293–295 [8] Kelly HW. Pharmaceutical characteristics that influence the clinical efficacy of inhaled corticosteroids. Ann Allergy Asthma Immunol 2003;91:326–34 [quiz 3435, 404]. [9] Badia L, Lund V. Topical corticosteroids in nasal polyposis. Drugs 2001;61:573–8. [10] Trow TK, Morris DG, Miller CR, et al. Granulomatous bronchiolitis of Crohn's disease successfully treated with inhaled budesonide. Thorax 2009;64:546–7. [11] De Cassan C, Fiorino G, Danese S. Second-generation corticosteroids for the treatment of Crohn's disease and ulcerative colitis: more effective and less side effects? Dig Dis 2012;30:368–75. [12] Bacharier LB, Raissy HH, Wilson L, et al. Long-term effect of budesonide on hypothalamic-pituitary-adrenal axis function in children with mild to moderate asthma. Pediatrics 2004;113:1693–9. [13] Kelly HW, Sternberg AL, Lescher R, et al. Effect of inhaled glucocorticoids in childhood on adult height. N Engl J Med 2012;367:904–12. [14] Roh HJ, Goh EK, Chon KM, et al. Topical inhalant steroid (budesonide, Pulmicort nasal) therapy in intubation granuloma. J Laryngol Otol 1999;113:427–32. [15] The Airway Reconstruction Team: recent challenges in the management of congenital tracheal stenosis: an individualized approach. J Pediatr Surg 2005;40: 774–80.
295
Discussion Discussant: Mark Powis (Leeds): Is there an optimal time for giving the budesonide? Do you use it once the granulation tissue has formed or can you use it prophylactically? Response: Dr Yokoi: Once we feel there is some obstacle at the tip of the tube then we look with bronchoscopy and if we see granulation then we start to use budesonide. Discussant: Abelbasit Ali (Sudan): Do you have any experience of using budesonide in patients with tracheal stenosis following repair of TOF? Response: Dr Yokoi: We are now using budesonide for tracheal granulation from all causes for example a tracheostomy for a wheeze in a mentally impaired patient or for sub-glottal stenosis. Once you see tracheal granulation budesonide is very effective.
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Treatment of postoperative tracheal granulation tissue with inhaled budesonide in congenital tracheal stenosis Akiko Yokoi a,⁎, Makoto Nakao a, Yuko Bitoh a, Hiroshi Arai a, Yoshihiro Oshima b, Eiji Nishijima a a b
Department of Pediatric Surgery, Kobe Children’s Hospital, Kobe, Japan Department of Cardiovascular Surgery, Kobe Children’s Hospital, Kobe, Japan
a r t i c l e
i n f o
Article history: Received 1 November 2013 Accepted 10 November 2013 Key words: Congenital tracheal stenosis Tracheoplasty Tissue granulation Inhaled corticosteroids
a b s t r a c t Purpose: Tracheal obstruction by granulation tissue can compromise the postoperative course in congenital tracheal stenosis (CTS). Balloon dilatation and stenting may be required. Budesonide is a corticosteroid with topical anti-inflammatory effects. In 2008, we used inhaled budesonide for treatment of postoperative granulation tissue for the first time in CTS, resulting in significant improvement. The aim of this study was to evaluate the efficacy of inhaled budesonide for treatment of postoperative granulation tissue in CTS. Methods: Retrospective chart review was conducted. From 2004 through 2011, we performed 39 tracheoplasties. Forced stenting ± balloon dilatation (S/B) was required when airway obstruction with tissue granulation was life-threatening. We compared the requirement for S/B between the early group without budesonide (2004–Nov. 2008, Early) and the late group with budesonide (Dec. 2008–2011, Late). Statistical analysis was performed using Fisher’s Exact test. Results: Eleven of 22 in Early and 8 of 17 in Late were successfully extubated, never having had lifethreatening tissue granulation. The remaining patients in each group (11 in Early and 9 in Late) required tracheostomies due to postoperative complication. Ten in Early and 5 in Late with tracheostomies developed granulation tissue. Of these patients, the 10 in Early required S/B, while none of the 5 in Late required S/B (P = .0003). Bronchoscopy demonstrated significant regression of granulation tissue in all cases treated with inhaled budesonide. Conclusion: Inhaled budesonide is effective for treatment of tracheal granulation tissue in patients with tracheostomies after repair of CTS. © 2014 Elsevier Inc. All rights reserved.
Congenital tracheal stenosis (CTS) is a relatively rare condition with high mortality rate. Slide tracheoplasty is the procedure of choice, especially for long segment of congenital tracheal stenosis [1]. Postoperative complications include bronchotracheal malacia, recurrent stenosis, and intraluminal tissue granulation [2–4]. These complications can cause life-threatening airway obstruction. The treatment of tissue granulation requires balloon dilatation and stenting [5,6]. Balloon dilatation causes tracheal wall disruption, resulting in a need for long-term stenting [7]. Intraluminal stenting also causes tube-tip granulation, again requiring balloon dilatation or laser ablation and deeper stenting. Inhaled budesonide is a corticosteroid with topical anti-inflammatory effect widely used as first-line therapy for asthma [8]. In 2008, we used inhaled budesonide for treatment of postoperative granulation for the first time in congenital tracheal stenosis, resulting in a significant improvement. Since then, we have routinely used inhaled budesonide for the treatment of tracheal granulation tissue. The aim
⁎ Corresponding author at: Kobe Children’s Hospital, Department of Pediatric Surgery, 1-1-1 Takakuradai, Sumaku, Kobe Japan. Tel.: +81 78 732 6961; fax: +81 78 735 0910. E-mail address: [email protected] (A. Yokoi). 0022-3468/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpedsurg.2013.11.041
of this study was to determine the efficacy of this treatment in preventing a significant cause of postoperative airway obstruction in congenital tracheal stenosis.
1. Materials and methods With the approval of the Kobe Children’s Hospital institutional review board (No.R25-1), retrospective chart reviews were conducted for surgically managed CTS in the period Jan. 2004 through Dec. 2011. A variety of surgical procedures were performed; these included tracheoplasties (standard posterior-anterior slide tracheoplasties and modified right-left slide tracheoplasties) and resection and end-toend anastomosis. Forced stenting ± balloon dilatation was performed when airway obstruction with tissue granulation was life-threatening. From December 2008, budesonide inhalation suspension (Pulmicort Respules®, AstraZeneca) 0.25 mg twice daily was used as the treatment of first choice for the management of tissue granulation after tracheoplasty. We compared the requirement for stenting, with or without balloon dilatation, between the Early group not receiving budesonide (from 2004 to November 2008) and the Late group with budesonide (December 2008 through 2011). Statistical analysis was
294
A. Yokoi et al. / Journal of Pediatric Surgery 49 (2014) 293–295
Table 1 Series of children with congenital tracheal stenosis (2004–2011).
Total Postoperative tracheostomy Tissue granulation Requiring stent with or without balloon dilatation
Early group (n)
Late group (n)
P value
22 11 10 10
17 9 5 0
1.00 0.13 b.0001
performed using Fisher’s exact test. Bronchoscopy was also performed before and after treatment with inhaled budesonide. 2. Results From Jan. 2004 through Dec. 2011, we performed 39 tracheoplasties (standard posterior-anterior slide tracheoplasties n = 30; modified right-left slide tracheoplasties n = 3; and resection and end-to-end anastomosis n = 6) for CTS. Eleven of 22 (50%) children in the Early group and 8 of 17 (47.1%) patients in the Late group were successfully extubated, never having had life-threatening tissue granulation. The other 11 and 9 children in each group required tracheostomies, due to postoperative bronchotracheal malacia or recurrent stenosis after tracheoplasty (P = 1.00). Ten out of 11 patients and 5 out of 9 patients in each group had intraluminal tissue granulation (P = 0.13). Stenting with or without balloon dilatation was required in 10 patients in the Early group, while none required stenting in the Late group (P b .0001) (Table 1). Bronchoscopy showed significant improvement with inhaled budesonide in the Late group (Fig. 1).
To address this, we initially used systemic or intratracheal steroids in an effort to regress intraluminal granulation. However, the observed efficacy of systemic steroids was limited, and long-term administration caused significant morbidity, such as bony fractures and infections. We subsequently used inhaled budesonide as first line therapy for tracheal tissue granulation after we observed the remarkable efficacy of this treatment in the first case in 2008. In all cases subsequent to 2008, tissue granulation regressed significantly in several days, avoiding forced stenting with balloon dilatation. Topical budesonide has been reported as an effective treatment for nasal polyps [9] and inflammatory bowel disease [10,11], with the advantage of effective local activity, minimized systemic toxicity, and limited adverse effects [12,13]. Roh et al. [14] reported the efficacy of inhaled budesonide in the treatment of intubation granulomas. Those reports suggested to us that budesonide could be an effective therapy for tissue granulation after tracheal reconstruction in patients with congenital airway stenosis. The Airway Reconstruction Team at the Hospital for Sick Children, Toronto [15] reported that tracheoplasty patients routinely received 24 hours of postoperative intravenous dexamethasone and inhaled budesonide, and “surprisingly” none developed intraluminal granulations, supporting the efficacy of budesonide for preventing tracheal granulation tissue. Inhaled budesonide could be used as prophylaxis of tracheal granulation in the patients who have postoperative tracheostomy. In conclusion, our experience suggests that inhaled budesonide can be effective for the treatment of tracheal granulation tissue, and may therefore provide an important option in the management of congenital tracheal stenosis.
References 3. Discussion Our study shows the efficacy of inhaled budesonide for the treatment of postoperative tracheal tissue granulation in CTS. Postoperative bronchotracheal malacia and recurrent stenosis may significantly compromise the tracheal lumen and thus patient safety, requiring long-term stenting. Tracheal granulation tissue, usually arising at the tip of the stenting tube, causes life-threatening airway obstruction, which is associated with high mortality rate in congenital tracheal stenosis. We had been treating intraluminal tissue granulation by inserting a stent deeper to bypass the granulation, with or without balloon dilatation, which in turn resulted in repeated and intractable deeper tube-tip granulation.
[1] Rutter MJ, Cotton RT, Azizkhan RG, et al. Slide tracheoplasty for the management of complete tracheal rings. J Pediatr Surg 2003;38:928–34. [2] Lang FJ, Hurni M, Monnier P. Long-segment congenital tracheal stenosis: treatment by slide-tracheoplasty. J Pediatr Surg 1999;34:1216–22. [3] Tsugawa C, Nishijima E, Muraji T, et al. Tracheoplasty for long segment congenital tracheal stenosis: analysis of 29 patients over two decades. J Pediatr Surg 2003;38: 1703–6. [4] Koopman JP, Bogers AJ, Witsenburg M, et al. Slide tracheoplasty for congenital tracheal stenosis. J Pediatr Surg 2004;39:19–23. [5] Elliott M, Hartley BE, Wallis C, et al. Slide tracheoplasty. Curr Opin Otolaryngol Head Neck Surg 2008;16:75–82. [6] Manning PB, Rutter MJ, Border WL. Slide tracheoplasty in infants and children: risk factors for prolonged postoperative ventilatory support. Ann Thorac Surg 2008;85:1187–91 [discussion 1191–1192]. [7] Wright CD. Treatment of congenital tracheal stenosis. Semin Thorac Cardiovasc Surg 2009;21:274–7.
Fig. 1. Child developing postoperative tissue granulation in the late group. Bronchoscopic findings before (A) and after (B) treatment with inhaled budesonide.
A. Yokoi et al. / Journal of Pediatric Surgery 49 (2014) 293–295 [8] Kelly HW. Pharmaceutical characteristics that influence the clinical efficacy of inhaled corticosteroids. Ann Allergy Asthma Immunol 2003;91:326–34 [quiz 3435, 404]. [9] Badia L, Lund V. Topical corticosteroids in nasal polyposis. Drugs 2001;61:573–8. [10] Trow TK, Morris DG, Miller CR, et al. Granulomatous bronchiolitis of Crohn's disease successfully treated with inhaled budesonide. Thorax 2009;64:546–7. [11] De Cassan C, Fiorino G, Danese S. Second-generation corticosteroids for the treatment of Crohn's disease and ulcerative colitis: more effective and less side effects? Dig Dis 2012;30:368–75. [12] Bacharier LB, Raissy HH, Wilson L, et al. Long-term effect of budesonide on hypothalamic-pituitary-adrenal axis function in children with mild to moderate asthma. Pediatrics 2004;113:1693–9. [13] Kelly HW, Sternberg AL, Lescher R, et al. Effect of inhaled glucocorticoids in childhood on adult height. N Engl J Med 2012;367:904–12. [14] Roh HJ, Goh EK, Chon KM, et al. Topical inhalant steroid (budesonide, Pulmicort nasal) therapy in intubation granuloma. J Laryngol Otol 1999;113:427–32. [15] The Airway Reconstruction Team: recent challenges in the management of congenital tracheal stenosis: an individualized approach. J Pediatr Surg 2005;40: 774–80.
295
Discussion Discussant: Mark Powis (Leeds): Is there an optimal time for giving the budesonide? Do you use it once the granulation tissue has formed or can you use it prophylactically? Response: Dr Yokoi: Once we feel there is some obstacle at the tip of the tube then we look with bronchoscopy and if we see granulation then we start to use budesonide. Discussant: Abelbasit Ali (Sudan): Do you have any experience of using budesonide in patients with tracheal stenosis following repair of TOF? Response: Dr Yokoi: We are now using budesonide for tracheal granulation from all causes for example a tracheostomy for a wheeze in a mentally impaired patient or for sub-glottal stenosis. Once you see tracheal granulation budesonide is very effective.