Intranasal steroids in adenoid hypertrophy and sleep disordered breathing in children
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Transcript of Intranasal steroids in adenoid hypertrophy and sleep disordered breathing in children
INS use in Adenoid hypertrophy and sleep disordered breathing in
children
Suparat Sirivimonpan,MD.
23/11/2012
Introduction
Intranasal corticosteroid(INS)
• since 1974• extremely effective in reducing the nasal
symptoms of sneezing, itching, rhinorrhea, and nasal congestion
• firstline treatment choice for patients with rhinitis, esp. persistent or more severe symptoms
• effective treatments for – AR,NAR , rhinosinusitis, and nasal polyposis– Adenoid hypertrophy?? , Snoring??, OSA ??
• nasal and oropharyngeal mucosal inflammation is present in patients with OSAS
Immunol Allergy Clin N Am 31 (2011) 545–560
Allergy 2008: 63: 1292–1300
• disorder of breathing during sleep characterized by – prolonged partial upper airway obstruction – and/or intermittent complete obstruction
(obstructive apnea) – that disrupts normal ventilation during sleep
and normal sleep patterns• prevalence of OSAS (Children) in the range of
1-5% (relatively common disease)
• obesity being an independent risk factor
OSAS (obstructive sleep apnea syndrome)
Pediatrics 2012;130:e714–e755
Pediatrics 2012;130:e714–e755
Seminars in Anesthesia, Perioperative Medicine and Pain (2006) 25, 109-116
Otolaryngol Clin N Am 45 (2012) 1055–1069
• Adenotonsillar hypertrophy is the most common cause of OSAS
• adenotonsillectomy (AT) : primary treatment recurrence
• postoperative PSG should be performed to ensure that OSAS has resolved
• postoperative complications : haemorrhage, airway obstruction secondary to edema, prolonged muscular paralysis and palato-pharyngeal insufficiency
OSAS
Pediatrics 2012;130:e714–e755
The Cochrane Library 2010, Issue 10
• CPAP was effective in the treatment of OSAS, but adherence is a major barrier
• In less severe cases, non-surgical interventions may be considered, however few medical alternatives are currently available
OSAS
Pediatrics 2012;130:e714–e755
The Cochrane Library 2010, Issue 10
Momethasone Furoate
Pediatrics 2007;119;e1392
• 2-stage, randomized, placebo-controlled trial• 60 children : AH and referred for exclusive
adenoidectomyExclusion criteria : -concomitant tonsillar hypertrophy-positive history of allergy or atopy-URI within the past 2 weeks-nasal anatomic anomalies-sinonasal diseases (ex. polyposis)-craniofacial malformations -genetic diseases-neurologic disorders-cardiovascular diseases-immunodeficiency-history of epistaxis-hypersensitivity to steroids -intranasal, topical, or systemic steroid or antibiotic treatment within the past 4 weeks
Inclusion criteria (1) adenoid pad occluding 75% of nasopharynx(nasal endoscopy)(2) age between 3 and 7 years(3) symptoms consistent with AH lasting 12 months(4) no previous adenoidectomy
Pediatrics 2007;119;e1392
Pediatrics 2007;119;e1392
group A30 patients
group B30 patients
60 patients
first stage
Mometasone (50 mcg/nostril/day)
placebo 40 daysassessment
Responders (21/27pts) (77%)second stage
group A1 11 pts
MF alternate days ,first 2 weeks per
month
group A2 10 pts
daily MF ,first 2 weeks per
month
3 months
Nonresponders and placebo-treatedPatients adenoidectomy
3 patients did not complete the study1: systemic steroid (acute ethmoiditis)1 : lost to follow-up monitoring1 : dropped out
• physical evaluation and nasal endoscopy• clinical history
– parents with a questionnaire– age, gender, weight, history and family history of
atopy or allergy, and use of drugs• Symptoms such as nasal obstruction, rhinorrhea,
cough, snoring, and obstructive sleep apnea were also – clinical scoring system ranging from 0 to 3 – (0 absent; 1 occasional; 2 frequent; 3 daytime
and nighttime symptoms)– score related to severity
• parents reported on their children’s symptoms and eventual adverse effects (eg, nasal bleeding)
• Compliance with drug administration was assessed biweekly in telephone interviews with parents
Pediatrics 2007;119;e1392
No patient -personal or family history of allergy or atopy -undergone previous surgery-received any drugs in the past 4 weeks-immunodeficiencies
Pediatrics 2007;119;e1392
• chronic nasal obstruction improved significantly in group A (mean overall symptom score: 3)
• unchanged in group B (mean overall symptom score: 9)
• Adenoid size also decreased significantly in patients given MF (mean choanal obstruction: 64%)
Pediatrics 2007;119;e1392
Pediatrics 2007;119;e1392
it is difficult to attribute the true value to theseresults because of the small number of patients studied
• no significant differences in symptom scores were observed between the 2 subgroups (A1,A2)
• mean choanal obstruction in group A2 was less than that in group A1 (56% vs 65.5%;P .001)
• daily administration of MF for 2 weeks per month seems to decrease AH further
• only 1 complication (episodic epistaxis)• Compliance with therapy during the last 3-month
period was satisfactory in both subarms
• Topical intranasal MF therapy can be considered a good therapeutic option to decrease AH
• Nasal administration is safe, reproducible, easily performed, and well tolerated by pediatric patients
• Daily use for 2 weeks per month after an initial 40-day-period treatment seems to be the ideal maintenance schedule
• indications for adenoidectomy remain unchanged for nonresponders
Conclusion
International Journal of Pediatric Otorhinolaryngology (2008) 72, 1171—1175
Pediatrics 2007;119;e1392
group A30 patients
group B30 patients
60 patients
first stage
Mometasone (50 mcg/nostrilday)
placebo 40 daysassessment
Responders (21/27pts) (77%)second stage
group A1 11 pts
MF alternate days ,first 2 weeks per
month
group A2 10 pts
daily MF ,first 2 weeks per
month
3 months
Nonresponders and placebo-treatedPatients adenoidectomy
3 patients did not complete the study1: systemic steroid (acute ethmoiditis)1 : lost to follow-up monitoring1 : dropped out
• maintenance therapy : MF aqueous nasal spray (50 mcg) in each nostril daily for first 2 weeks of every month
• During follow-up visits, parents or legal guardians reported – duration of maintenance therapy – eventual adenoid surgical treatment
• Based on this information, divided into 3 subgroups: (1) children voluntarily suspending maintenance therapy and requiring surgery (Group A)(2) children continuing maintenance therapy but needing surgery (Group B)(3) children continuing maintenance therapy but not undergoing surgery (Group C)
International Journal of Pediatric Otorhinolaryngology (2008) 72, 1171—1175
• assessment performed after first 4 months of treatment (previous trial) clinical and endoscopic baseline
• clinical picture including nasal obstruction, rhinorrhea, cough, snoring, and obstructive sleep apnea, and adenoid size were evaluated before the surgical procedure and at the last follow-up visit in the surgical groups
• clinical and/or endoscopic evaluation– Nasal chronic obstructive symptoms : clinical
score (0-3)– AH size was assessed by means of nasal
endoscopyInternational Journal of Pediatric Otorhinolaryngology (2008) 72, 1171—1175
• 21 children : responders - included in study• 12 males and 9 females• mean age of 7±1.6 years
International Journal of Pediatric Otorhinolaryngology (2008) 72, 1171—1175
A : surgery , no INS : 6 pts B : INS and Surgery : 3 ptsC : INS , no surgery : 12 pts
International Journal of Pediatric Otorhinolaryngology (2008) 72, 1171—1175
Group C : - further significant improvement -Maintenance therapy was stopped definitively after a mean period treatment of 23 months (range: 15—31 months)
Group A : voluntarily suspended maintenance therapy within a few months (range: 1—3 months) after the first period of treatment
Group B : - 2 adenoidectomy , 1 patients adenoidectomy combined with transtympanic drainage - nasal endoscopic examination revealed mild AH close to the Eustachian tube - Chronic obstructive nasal symptoms and adenoid pad size were unchangedcompared to baseline data
• Intranasal MF treatment was broken off due to poor compliance by parents or legal guardians (group A)– significant worsening of nasal chronic obstructive
symptoms and an increase of adenoid size surgical treatment
• regular continuity successful results• longterm therapy is safe and well tolerated by pediatric
patients– No side effects were observed after a mean follow-up
of 28 months (range: 6—36 months)
• A multicenter, prospective, randomized study is warranted to confirm definitively the efficacy of nasal MF
International Journal of Pediatric Otorhinolaryngology (2008) 72, 1171—1175
Clinical and Experimental Otorhinolaryngology Vol. 4, No. 1: 27-32, March 2011
mometasone furoate
• prospective, observational study• 2-11 year-old children• Sleep-disordered breathing (SDB) : ranging from primary snoring
to OSAS
Inclusion criteria• 1) history of habitual snoring for the last 3 months or longer• 2) adenoid hypertrophy confirmed with simple X-ray findings or
endoscopic examination by otolaryngologist
Exclusion criteria• 1) presence of symptoms of acute respiratory infection• 2) use of nasal or systemic corticosteroid or antibiotics within 4
weeks prior to the study• 3) prior tonsil or adenoid surgery• 4) history of craniofacial, neuromuscular, or genetic disorders
Clinical and Experimental Otorhinolaryngology Vol. 4, No. 1: 27-32, March 2011
• All patients received 4 weeks course of single intranasal administration in each nostril with mometasone furoate (100 μg)
• Assessment : – history and physical examination (BW,height)– parental questionnaire (OSA-18)– sinus Xray, adenoid X-ray– skin prick test or Pharmacia CAP system for detecting
allergy
• Allergic rhinitis was diagnosed in case that each child complaining typical allergic symptoms showed positive result in allergic test
• After 4 weeks course re-assess
Clinical and Experimental Otorhinolaryngology Vol. 4, No. 1: 27-32, March 2011
Clinical and Experimental Otorhinolaryngology Vol. 4, No. 1: 27-32, March 2011
Clinical and Experimental Otorhinolaryngology Vol. 4, No. 1: 27-32, March 2011
Clinical and Experimental Otorhinolaryngology Vol. 4, No. 1: 27-32, March 2011
Clinical and Experimental Otorhinolaryngology Vol. 4, No. 1: 27-32, March 2011
• presence of allergy (P=0.065) and obesity (P=0.851) didn’t affect the effect of nasal steroid on total OSA-18 score
• no significant change in body weight between before and after treatment (P=0.954)
• Change in OSA-18 score showed no significant difference according to presence of sinusitis (P=0.488)
Clinical and Experimental Otorhinolaryngology Vol. 4, No. 1: 27-32, March 2011
Clinical and Experimental Otorhinolaryngology Vol. 4, No. 1: 27-32, March 2011
• could not have a control group due to lack of consent
• didn’t confirm the increased nasal airway patency with objective tool – under 5 years old impossible to get
patient’s cooperation during acoustic rhinometry
Limitation
Clinical and Experimental Otorhinolaryngology Vol. 4, No. 1: 27-32, March 2011
• 4-weeks course of INS (mometasone furoate) can be a effective treatment option in pediatric SDB patients without significant complications
• this treatment works effectively regardless of allergic status, sinusitis, and obesity
• improvement in quality of life of SDB children is due to not only decreased AN ratio but also other factors such as increase nasal airway patency
• Considering this result, intranasal steroid can be used in SDB children regardless of allergic status or sinusitis
Conclusion
Clinical and Experimental Otorhinolaryngology Vol. 4, No. 1: 27-32, March 2011
International Journal of Pediatric Otorhinolaryngology 76 (2012) 829–831
• study aims : – compare the effect of environmental
prophylaxis and nasal saline douching to nasal mometasone furoate in children with adenoid hypertrophy, regarding: • improvement of specific respiratory and
nasal symptoms • objective reduction of adenoid tissue area
• Children aged 4–8 years with previous diagnosis of adenoid hypertrophy
International Journal of Pediatric Otorhinolaryngology 76 (2012) 829–831
• Inclusion criteria – symptoms of nasal obstruction and snoring and
previous nasoendoscopy or lateral X-ray suggestive of adenoid hypertrophy
• Exclusion criteria – use of topical or systemic corticosteroid, antihistamine
or antibiotics for at least 2 months at first consultation– viral or bacterial upper airways infection at the previous
month– Immunodeficiency– patients with nasal septal deviation– systemic diseases, such as cystic fibrosis or facial
malformation
International Journal of Pediatric Otorhinolaryngology 76 (2012) 829–831
• questionnaire on the symptoms nasal obstruction, snoring, rhinorrhea, sneezing and itching
• all the children : prick test for respiratory allergens, nasoendoscopy
International Journal of Pediatric Otorhinolaryngology 76 (2012) 829–831
NSS douching + environmental prophylaxis (general and specific allergens) 40
days
0 (absent)1 (mild)2 (moderate) 3 (severe)
symptoms questionnaire and to nasoendoscopy
topical mometasone furoate (50 mcg/(nostril day) 40 days
symptoms questionnaire and to nasoendoscopy
adenoid area in relation to the nasopharyngeal area
main purpose of this study design was to minimize the interference of confusing external macro-environment factors(such as home, school, habits and exposure to allergens)
• 60 children were initially selected • 51 concluded the study
– 34 (66.6%) males VS 17 (33.3%) females– Mean age (SD) was 6.43±1.47
– 24 patients (47.05%) : positive prick test to at least one allergen,
– 27 (52.95%) : non-atopic
International Journal of Pediatric Otorhinolaryngology 76 (2012) 829–831
severe obstruction
MF significantly decreased from priortreatment and after saline douching (obstruction and snoring)
International Journal of Pediatric Otorhinolaryngology 76 (2012) 829–831
moderate irritative nasal symptoms
MF significantly decreased from priortreatment and after saline douching (obstruction and snoring)
International Journal of Pediatric Otorhinolaryngology 76 (2012) 829–831
NSS irrigation : reduction was not significantly different from before treatment
MF : significantly lower than that detected at the other twotime points
International Journal of Pediatric Otorhinolaryngology 76 (2012) 829–831
Nasal douching and environmental prophylaxis
• Significantly improved nasal symptoms, snoring and all related symptoms due to improved nasal clearance, decreased mucosal
edema and increased nasal permeability.• but did not influence on adenoid tissue area
Conclusion
Mometasone furoate •additionally improved clinical symptoms and reduced adenoid hypertrophy when compared to exclusive nasal saline douching combined with environmental prophylaxis;•also significantly reduced the adenoid area in relation to the nasopharynx, in an objective evaluation
Fluticasone propionate
• prospective, randomized, placebo-controlled study
Inclusion criteria• adenotonsillectomy-indicated patients • having symptoms associated with adenoid
hypertrophy for at least 6 months
International Journal of Pediatric Otorhinolaryngology 74 (2010) 773–776
Exclusion criteria• adenoidectomy previously• URI or allergic rhinitis or turbinate hypertrophy• had taken intranasal topical or systemic steroid in the last 1
year• taken any intranasal medical treatment• history of chronic nose-bleeding• Immunodeficiency• history of hypersensitivity, positive allergy or atopy against
fluticasone• tonsillar hypertrophy• chronic otitis media with effusion • anatomic deformity in noise or sinonasal diseases • Craniofacial abnormalities such as cleft lip/cleft palate• genetic diseases (Down Syndrome)• neurological diseases • cardiovascular diseases
International Journal of Pediatric Otorhinolaryngology 74 (2010) 773–776
• randomly divided into two groups– fluticasone propionate nasal drops of 400
mcg/day for 8 weeks (NSD- nasal steroid drop)
– normal saline (NS) in the same way• follow-up every 4 weeks• No patient discontinuation occurred during the
study
International Journal of Pediatric Otorhinolaryngology 74 (2010) 773–776
• symptoms of nasal airway obstruction were assessed (0,8 wk)• fiberendoscopic images or rigid nasal endoscopic
images
• using the nasal passage way, choanal openings from top to bottom were graded (grade 1–4) – 1st grade: only top segment of choana is obstructed <%25– 2nd grade: upper half of the choana is obstructed <%50– 3rd grade: lying to the rhinopharynx and tuba opening is
partially obstructed <%75– 4th grade: choana is almost completely obstructed
International Journal of Pediatric Otorhinolaryngology 74 (2010) 773–776
International Journal of Pediatric Otorhinolaryngology 74 (2010) 773–776
• Before the treatment there was no statistically significant difference between the NSD and NS group
• Statistically significant improvement (p < 0.05) was observed in the NSD treated group compared to the NS treated group
International Journal of Pediatric Otorhinolaryngology 74 (2010) 773–776
no statistically significant difference observed between the two groups, in terms of their tonsil size
NSD treatment• 19/25 patients(76%) : no longer a need for surgery• Adenoidectomy 3 patients (12%)• 3 patients (12%) were informed of their ongoing need for
surgery but their parents refused the surgery declaring that NSD had sufficiently improved their conditions
Normal saline treatment • 16/20(80%) : need for surgery • 4 patients postponed their adenoidectomy at the request
of their parents for further monitoring in spite of persistant surgical indication
International Journal of Pediatric Otorhinolaryngology 74 (2010) 773–776
• Improvement in nasal airway obstruction symptoms – effect of intranasal corticosteroids on adenoid size– reduce soft tissues of inferior turbinate
• Intranasal steroid in drop form provides a better spread in the nasal cavity and reaches the nasopharynx and pharynx faster
• Disadvantages : application position is uncomfortable• No complaints regarding usage have been reported
by the patients in this study
• only 1 case of episodic nose-bleeding and 1 sneezing
International Journal of Pediatric Otorhinolaryngology 74 (2010) 773–776
• This method provides an effective alternative to surgical treatment in children with adenoid hypertrophy
• Intranasal corticosteroids are well tolerated by children
• however, the most appropriate drug, the most efficient dose and optimal treatment duration continue to be investigated and determined by way of further prospective and randomized studies
Conclusion
International Journal of Pediatric Otorhinolaryngology 74 (2010) 773–776
Budesonide
Pediatrics 2008;122:e149–e155
• randomized, double-blind, crossover design
Inclusion criteria• Children 6-12 years• habitual snoring, and on initial overnight
polysomnographic assessment (PSG-1) fulfilled the criteria for mild OSAS– AHI 3-7 per hour of TST – Or AHI of 2 per hour of TST but in the presence of a
respiratory arousal index (RAI) of 2 per hour of TST and nadir oxygen saturation 85%
Pediatrics 2008;122:e149–e155
Exclusion criteria • asthma that required chronic preventive therapy• hypersensitivity to budesonide• recent nasal trauma• nasal surgery or nasal septum perforation• Current therapy with drugs that interact with budesonide
(erythromycin, clarythromycin, ketoconazole, and cimetidine)• known immunodeficiency or undergoing immunosuppressant
therapy • craniofacial, neuromuscular, syndromic, or defined genetic
abnormalities• URI; systemic corticosteroidtherapy; or antibiotic therapy in
the 2 weeks before the initiation of the study• children who already had had T&A in the past 12 months
Pediatrics 2008;122:e149–e155
Patients with a history of allergic rhinitis were also included
placebo spray [saline]) OD
Pediatrics 2008;122:e149–e155
topical budesonide (32mcg/puff/nostril[total 64 mcg]
N=43
19 withdraw (14 placebo ,5 budesonide)
Total 62
7 unwillingness to continue INS6 marked improvement (5/6 budesonide) 6 decided to pursue T&A (all placebo)
Pediatrics 2008;122:e149–e155
antihistaminic medications or immunotherapyfor allergic symptoms was recorded for 23 children
Pediatrics 2008;122:e149–e155
intranasal budesonide : -significant improvements in several PSG abnormalities, namely OAHI, RAI, and nadir SpO2-along with significant changes in some measures that pertain to sleep macroarchitecture, such as sleep latency, and the percentage of TST spent in either slow-wave sleep or rapid-eye-movement sleep
Pediatrics 2008;122:e149–e155
Significant reductions in adenoid size occurred with decreases in adenoidal nasopharyngeal ratio (N/P) ratio from 0.71±0.02 before treatment to 0.57±0.02 after 6 weeks of budesonide therapy (P .0001)54.1% children had normalization of their OAHI on the basis of currently accepted criteria
(ie, OAHI 1 per hour of TST)
• No differences in the responses to treatment either for – Obese versus nonobese children or – among children who had a history of allergic
symptoms as compared with those who did not report any allergic problems
Pediatrics 2008;122:e149–e155
Pediatrics 2008;122:e149–e155
18
no significant changes emerged during this follow-up period in PSG characteristics, degree of respiratory disturbance, or adenoid size
• Intranasal budesonide administered during a period of 6 weeks to children with mild OSA effectively alleviated severity of respiratory disturbance, reduced size of adenoid tissues, and significantly improved, albeit slightly, some components of sleep architecture
• discontinuation of the therapy for a period of 8 weeks did not seem to be associated with worsening of sleep or respiratory parameters
Pediatrics 2008;122:e149–e155
study design
Partici-pant
Rx control duration
outcome
Berlucchi2007
RCT ,2 stage
AH 60(3-7 yr)
1st ST: MF 1x12nd ST: MF daily 2 wks/mo
1st ST: placebo2nd ST: MF alternate days 2 wk/mo
1st stage: 40 days
2nd stage: 3 months
Reduce in clinical symptom score
and adenoid size
Yong Gi Jung 2001
Prospec-
tive
SDB 41(2-11 yr)
MF 1x2 no 4 wk improve SDB, physical symptom,
adenoid size
Renaldo2012
Prospec-
tive
AH 51(4-8 yr)
1st ST : NSS+Env.2nd ST : MF 1x1
no 4wk4 wk
Reduce nasal symptom score
and adenoid size
Demirhan 2010
RCT AH 45(4-16 yr)
FP drop 400 mcg/day
NSS 8 wk Reduce nasal obstruction,
snoring, apnea, adenoid size
Gozal 2008
RCT,crossov
er
Mild OSAS 62
(6-12yr)
BD 1x1 NSS 6 wk Improve respiratory
disturbance, reduce adenoid
size
Otolaryngology -- Head and Neck Surgery 2009 140: 139Otolaryngology -- Head and Neck Surgery 2009 140: 139
Otolaryngology -- Head and Neck Surgery 2009 140: 139
• The available evidence suggests that nasal steroids may significantly improve symptoms of nasal obstruction in children with adenoid hypertrophy
• The effect of nasal steroids on adenoid hypertrophy appears to be a group effect, not specific to any particular steroid (MF,FP,BD,Beclo,flunisolide) (TA,FF??)
• Nasal steroids appear to be safe and well tolerated in children nonsurgical management option attractive
• more robust high-quality randomized controlled studies are needed to confirm the results
• focus on optimal duration of treatment, minimum effective dosage, long-term efficacy, and the safety of long-term maintenance therapy
Conclusion
• What is the optimal duration of intranasal steroid use? • All trials have been short-term with a short-term
follow-up• Does the OSAS recur on discontinuation of therapy? • What is the efficacy of intranasal steroids in children
who have chronic or atopic rhinitis?• How do the benefits and adverse effects of long-term
nasal steroids compare with surgery?• Do they correlate with clinical outcomes or long-term
prognosis?
Areas for Future Research
Thank you