1. SUCCESFULL TREATMENT OF SUBGLOTTIC HAEMANGIOMAS WITH PROPRANOLOL
Gács É, Katona G, Uhereczky G, Szabó L Heim Pál Children’s Hospital, Budapest
Chairmen , dear collegues.
In this section – beeing pediatric pulmologist- I am the odd one out. I am working in Hungary,s biggest children Hostpital , our department is specialised in airway diseases. So we have also patient with airway haemangioma, and manage them together with ENT collegiues.

2. DEPARTMENT OF PULMONOLGY
Heim Pál
Children’s Hospital
Budapest, Hungary
First , let me show our hospital , this our building, and departement
DEPARTMENT OF PULMONOLGY

3. DEPARTMENT OF PULMONOLGY
Heim Pál Children’s Hospital
Budapest, Hungary
DEPARTMENT OF PULMONOLGY
15 BEDS
3 OUTPATIENT ROOMS
5 PULMOLOGISTS 7000 PATIENT /YEAR (asthma, wheezy bronchitis,cystic fibrosis…)
CLINICAL STUDIES
MAIN INTERESTS ASTHMA-CARE
QOL
PATIENT EDUCATION:
meetings, books,website
Everything of asthma:
for patients and parents
We have 15 beds for pulmonary diseases, and 3 outpatient rooms with 5 pulmologists, a lot of patient. Our main interest are: asthma care, find very importan the patient education , that,s why we organise meetings, writing books and website.
And now, let.s see my topic:

4. Haemangioma
beningn vascular tumors most commonly encountered in infancy
incidence: 5-10 % at the end of the first year
Increased risk in premature neonates and in females
most of them regress spontaneously
Infantile hemangioma, a benign vascular tumor, is the most common tumor of infancy, with an incidence of 5%–10% at the end of the first year. There is increased risk in premature neonates and in females. Most of has a spontan regression, and so
The tumor displays a distinctive life cycle that can be separated, both clinically and histologically, into three phases: the proliferating phase starts within a few weeks from birth and ends within the first year of life, with the most growth occurring during the first 4–6 months of life.
The involuting phase typically begins at 1 yr of age. Finally, at the involuted phase, tumor growth has stopped and the tumor has regressed. The regression is either complete or, more often, leaves scar tissue, telangiectasia, or redundant or anetodermic skin

5. Treatment In most patient no specific treatment is required
In 10% of cases haemangioma has excessiv growth, or has problematic location
Subglottic haemangiomas are rare but can be life-threatening in proliferation phase, during the first 4-6 months of life
Corticosteroids have been the first-line treatment for IH for more than 40 years.
….. in most patients no specific treatment is required. However, in 10% of cases IH is problematic or even dangerous for he child, becaouse of excessiv growth or its location . That is the case with subglottic haemangiomas, . This manifestation is rare, but can be life treatening in proliferation phase. For more than 40 years the first line treatment was corticosteroids .
In these circumstances that carry the risk of irreversible disfigurement, airway obstruction, or decreased vision, treatment is indicated. In recent years, beta-blockers, most specifically propranolol, have been shown to be an effective pharmacological treatment of proliferating IH.

6. The propranolol story
There has been a dramatic evolution in the treatment of laryngotracheal haemangiomas
2008 discovery by „chance” of the effectiveness of propranolol (Léaute-Labreze)
A french group discovered by chance, the good effect of propranolo, and so the propranolol story begun.

7. Effect of propranolol:
vasoconstriction
downregulation of proangiogenetic factors:
VEGF – vascular endothelial growht factor
BFGF- basic fibroblast growht factor
apoptosis of capillary endothelial cells
This good effect has tree elements:
First, there is a rapid effect because os vasoconsctriction, and than comes - for several monts- the downregulaion os proangiogenetic factors: namely vascular endothelial grows factor and basic fibroblast growht factor. At the end apoptosis of capillary entothelial cells occurs.

8. First patient: girl, born 17-09-2010
Haemangioma on left arm, palm, and lips
Respiratory symptoms since one month: Inspiratory stridor Stenotic cough
Let me talk about our first patient, this girl had haemangioma on left arm, palm, lips, and respiratory symptoms inspiratory stridor and stenotic cough since the age of one monts.
With permission of parents

9. Bronchoscopy
On bronchoscopic picture you can see the serious subglottic stenosis

10. Therapy: Oxygen intermittent Epinephrine inhalation Steroid 1 mg / kg
Propranolol: 2mg/kg/day
She was given oxygen, epinephrin inhalation and steroid with moderate effect , than propranolol was started.

11. Modified Westley croup-score
Inspiratoric stridor
Intercostal retraction
Jugular retraction
General condition
Cough
0- 15
We created a modified score to evaluate the improvement , with this five condition , and between zero and fiveteen points

12. Symptom-score: days epinephrin steroid propranolol end of steroid
This picture clearly shows, that epinephrin and sterois had a moderate effect, but after giving propranolol, the syptome score showed a rapid decline. Actually it was incredible for me for the first time
days
epinephrin
steroid
propranolol
end of steroid

13. Improvement in endoscopic picture
Beside the clinical improvement, there was a clear endoscopic improvemnt too, after two months and 9 months of treatment

14. 4 patients in our department
A.S.
V.H.
M.M.
Sz.Z.
age (months) 2
stridor ++ +
+++
cough
skin
lips, arms -
face, lips
lips
duration of P.therapy (months) 16 6 18 12
steroid
2 weeks
4 months
surgical intervention
side-effects
bradycardia
In the last 7 years we have 4 patiens with serious subglottic stenosis , All of them were 2 months old, girl, had stenotic cough, no needfor surgical intervention . The shortest Propranolol treatment was given patient 2., she had noskin symptom, and the longest treatment was 18 months ( patient 3) , together with a long steroid treatment too. Side-effect ( temporary bradycardia) occured in patient 4.

15. After propranolol treatment
A.S.
V.H.
M.M.
SZ.Z.
Month after cessation of P. 60 24 6
stridor -
cough
occasionally
skin
better
Somatic development
good
slow
steroid
occasionally (last steroid in 2015)
Surgical intervention
This picture shows our follow-up period after treatment ( between half és 5 years) We can say, the girls are well.With no respiratory and mild skin symptoms

16. Skin symptoms of patient No3. before treatment
She is our patient three, she had the most impressive skin symptoms and needed the longest treatment.
With permission of parents

17. … and now (7 years old)
After 7 years she has mild skin symptoms with no respiratory symptoms.
With permission of parents

18. SUMMARY
Carefully administered, propranolol may demonstrate efficacy as a first-line agent in most cases avoiding surgery, tracheostomy or prolonged steroids.
However, some lesions may be partly resistant to propranolol and require surgery or long-term steroids.
So, in summery:
1. F. Denoyelle et al: International Journal of Pediatric Otorhinolaryngology 73 (2009) 1168–1172
2.N.Raol et al: International Journal of Pediatric Otorhinolaryngology (2011)
3.L.R.Javia et al: International Journal of Pediatric Otorhinolaryngology 75 (2011) 1450–1454

19. Thank you for your kind attention.