Chronic rhinosinusitis in children Presented by Anchalee Senavonge, MD. October7, 2016

1. Chronic rhinosinusitis
in children
Anchalee Senavonge MD.
Pediatric Allergy and Immunology department
Chulalongkorn University

2. Definition
Middletion textbook 8th edition, European position paper 2012

3. Definition
Diagnosis and Management of Rhinosinusitis: Highlights from the 2015 Practice Parameter
Recurrent ARS: at least 3 episodes of ABRS in 1 yr

4. Phenotypes of CRS
Ann Allergy Asthma Immunol 117 (2016)

5. Development of sinuses
• Maxillary sinus-1st , begin pneumatization from birth to 12 mo
• Ethmoid: present at birth, reach adult size 12-14 yr
• Frontal and sphenoid: later, complete pneumatization at mid
to late adolescence
Diagnosis and management of rhinosinusitis: a practice parameter 2014

7. Diagnosis and management of rhinosinusitis: a practice parameter 2014
Ostiomeatal complex

8. Sinus physiology
• Pseudostratified, ciliated columnar epithelia interspersed with
globlet cells
• Obstruction mucous impaction and ↓oxygenation
▫ limited gas exchange  ↓ oxygen concentrations anaerobic
condition  bacteria growth
▫ ↓ Air pressure  causes pain and pressure sensation
• Acute purulent sinusitis- ↑pressure pain due to inflammation of
the mucosa and pressure from intra-sinus secretions
• Role of biofilm: “mortar” composed of a bacterially extruded exo-
polymeric matrix (protein and nucleic acid)
Diagnosis and management of rhinosinusitis: a practice parameter 2014

9. Microbiology in CRS
Adults
• Aerobes: Streptococcus species
(21%), H influenzae (16%), P
aeruginosa (16%), S aureus
(10%), and M catarrhalis (10%).
• Anaerobes: Prevotella species
(31%), Streptococci (22%),
Fusobacterium(16%).
Children
• Alpha-hemolytic streptococcus
(20.8%), H influenzae (19.5%),
S pneumoniae (14.0%), S
epidermidis (13.0%), and S
aureus (9.3%).
• Anaerobes were recovered from
8.0% of all isolates
Bacteriologic findings associated with
chronic bacterial maxillary sinusitis in adults. Clin Infect Dis. 2002
Maxillary sinus puncture with endoscopic middle meatal culture
in pediatric rhinosinusitis.Am J Rhinol. 2008

10. Microbiology in CRS
Nosocomial rhinosinusitis
• gram-negative enteric species
(eg, P aeruginosa, Klebsiella
pneumoniae, Enterobacter
species, Proteus mirabilis, and
Serratia marcescens)
• gram-positive cocci (occasionally
streptococci and staphylococci)
CRSwNP
• Polymicrobial aerobic and
anaerobic flora
Bacteriology of chronic maxillary sinusitis associated
with nasal polyposis. J Med Microbiol. 2005
Nosocomial sinusitis: a unique subset of sinusitis.
Curr Opin Infect Dis. 2005;

11. Clinical manifestation

12. History
• Persistent cough, prolonged anterior and posterior
nasal drainage, congestion
• low-grade fever, irritability, and behavioral difficulties
• Headache, especially in the frontal area, is a less
common
• Frequent URI or recurrent sinusitis
• Additional history should focus on identification of
any potential contributing factors
CRS in children. Pediatr Clin N Am 2013

13. Physical examination
CRS in children. Pediatr Clin N Am 2013

14. Approach to CRS

15. Diagnosis and management of rhinosinusitis: a practice parameter 2014

17. Diagnosis and management of rhinosinusitis: a practice parameter 2014

19. Medical treatment of pediatric chronic rhinosinusitis. Am J Rhinol Allergy 2016

20. Stepwise evaluation of CRS
CRS Epidemiology and medical management. JACI 2011

21. Contributing factors in CRS
CRS in children. Pediatr Clin N Am 2013

22. Approach to CRS
CRSsNP CRSwNP
• Anatomical defect/ variation
• Trauma, foreign body
• Environmental triggers
• Allergy
• Immunodeficiency
• GERD
• Eosinophilic mucin RS (EMRS)
• Aspirin intolerance
• Allergic fungal RS (AFRS)
• Cystic fibrosis
• Primary ciliary dyskinesia

23. Structure defect
• Septal deviation, Haller cells, paradoxical curvature
of the middle turbinate, and agger nasi cells
▫ predispose to obstruction of the ostiomeatal unit,
development of CRS, or both
CRS Epidemiology and medical management. JACI 2011

24. Environmental triggers
• Pollution: carbon monoxide, nitrous dioxide, sulfur
dioxide
• Irritants in air pollution: sulfur dioxide ozone and
formaldehyde (indoor pollutant)
• Hay fever
• Indoor dampness and mold exposure
• Active and secondhand cigarette smoking
CRS Epidemiology and medical management. JACI 2011

25. Allergic/ nonallergic rhinitis
• Congestion interfere drainage, ↑secretionhypoxic and
acidosis leads to mucociliary dysfunction bacteria multiply
• CRS 36-60% have AR children, 40-84% in adult
• CRS with AR likely to have persistent disease despite FESS
• Test: SPT, specific IgE
Diagnosis and management of rhinosinusitis: a practice parameter 2014

26. Sinusitis-asthma
• การสูดสารคัดหลั่งจากไซนัสลงไปในปอด
• การกระตุ้นผ่านประสาทสมองคู่ที่ 10 เกิดreflex bronchospasm
• การหายใจทางปากทาให้เกิดภาวะหลอดลมแห้งและกระตุ้นการ สร้างสารที่มีฤทธิ์
ทาให้หลอดลมตีบโดยตรง
• การกระตุ้นผ่านทางเซลล์ชนิดต่างๆ ที่เกี่ยวกับการอักเสบ เช่น ทาให้
eosinophils เข้าไปในเยื่อบุของทางเดินหายใจทั้งในไซนัสและหลอดลมมาก
ขึ้น
เอกสารประกอบการประชุมวิชาการประจา 2559 สมาคมสภาองค์กรโรคหืดแห่งประเทศไทย

27. เอกสารประกอบการประชุมวิชาการประจา 2559 สมาคมสภาองค์กรโรคหืดแห่งประเทศไทย

28. Immunodeficiency
• “Humoral”
• Other:
▫ Ataxia
telangiectasia,
WAS, C3
deficiency
Immunodeficiency in chronic sinusitis. Am J Rhinol Allergy 2015
Infectious CRS, JACI 2016

29. Immunodeficiency
• Test
▫ IgA, IgM, IgG, specific Ab level to polysaccharide vaccine
and tetanus/Diphtheria, flow cytometry, level of
complement
▫ IgG subclass not typically recommended
Immunodeficiency in chronic sinusitis. Am J Rhinol Allergy 2015

30. Immunoglobulin deficiency in patients with CRS: Systematic review of the literature and meta-analysis. JACI2015
Immunodeficiency-Systematic review

31. Immunodeficiency CRS in children
• Shapiro et al
• 34 of 61 children with refractory sinusitis
• decreased IgG3 levels and poor response to
pneumococcal antigen -most common
CRS Epidemiology and medical management. JACI 2011

32. • 94 children with RARS
• Mean age 7.7+_2.6 yr
• 6 patients not respond
to other therapy -->
received IVIg, 4/6
responded
Clinical characteristics of recurrent acute rhinosinusitis in children.
Asian Pac J Allergy Immunol 2015
Immunodeficiency-Siriraj study

33. CRSwNP
Middletion textbook 8th edition

34. • Eosinophils staining positive for the anti–eosinophil cationic protein (ECP)
antibody EG2: prominent and characteristic finding 80% of polyps
• Lymphocytes and neutrophils: predominant in CF and PCD
Ann Allergy Asthma Immunol 117 (2016)
CRSwNP

35. Allergic fungal rhinosinusitis (AFRS)
• CRSwNP with characteristic eosinophilic mucin
• semisolid nasal crusts that are similar to allergic mucin-peanut
butter like
• presence of fungi in the mucin by staining or culture
• Most common: Bipolaris, Curvalaria, Aspergillus, Drechslera
species
Diagnosis and management of rhinosinusitis: a practice parameter 2014
CRS Epidemiology and medical management. JACI 2011

36. AFRS
1. Opacified sinus cavities despite
extensive medical therapy
2. Characteristic CT
hyperdensities within the
opacified sinuses, which
suggest accumulated allergic
mucin
3. Evidence of IgE-mediated
allergy
CT scans : opacified nasal cavities and paranasal sinuses
‘‘hyperdensities'' within the opacified sinuses, as well as local
and linear areas of increased density within the nasal cavities.
CRS Epidemiology and medical management. JACI 2011

37. AFRS

38. Cystic fibrosis
• Mutations in CFTR on chromosome 7
• ↓Chloride ion secretion result in
▫ ↑secretion viscosity
▫ also -dilation of glandular ducts,↑ submucosal gland,↑ surfactant
gene expression
• Suspect when
▫ CRS in young ages (< 6 yr)with nasal polyps (40%)
▫ Pseudomonas aeruginosa, Burholderia capacia colonization
▫ chronic lung infection, pancreatic insufficiency
• Test: Gibson-Cooke sweat test or quantitative pilocarpine iontophoresis
DNA analysis
Medical treatment of pediatric chronic rhinosinusitis. Am J Rhinol Allergy 2016
Diagnosis and management of rhinosinusitis: a practice parameter 2014

39. Ciliary dysfunction
• Primary ciliary dyskinesia (Kartagener syndrome)
• rare AR disorder 10 per million
• Suspect when
▫ recurrent otitis media, CRS, pneumonia wih bronchiectasis
▫ situs inversus, sterile
• Test: screen-nasal nitric oxide (low in PCD) and the saccharine
test, definite-transmission electron microscopy
Diagnosis and management of rhinosinusitis: a practice parameter 2014

40. CRSwNP Clinical clues
Eosinophilic mucin
RS
• eosinophilic mucin, co-morbid asthma
• CT opacity
AERD • multiple polyps, rapid growth
• Samter triad
• universal recurrence after surgery
AFRS • often unilateral/limited to 1 or a few sinus cavities
• eosinophilic mucin with fungal hyphae and fungal allergy
• CT opacity, hyperdensities and bony erosion
CF • <6yr
• neutrophilia suggesting the high prevalence of acute
superinfections
• Pseudomonas aeruginosa or Burkholderia cepacia
• chronic lung infections or pancreatic insufficiency
Kartagener
syndrome
Neutrophil, sinus inversus, recurrent otitis media,
bronchiectasis

41. Management of CRS

42. Medical treatment of pediatric chronic rhinosinusitis. Am J Rhinol Allergy 2016

43. Medical treatment of pediatric chronic rhinosinusitis. Am J Rhinol Allergy 2016

44. Management in CRS
• Medical
▫ Systemic antibiotic
▫ Glucocorticoids
▫ Combination systemic
antibiotics and steroid
▫ Topical steroid irrigations
▫ Saline irrigations
▫ Antihistamines
▫ Leukotriene modifiers
▫ Antifungal drugs
• Surgical
▫ Adenoidectomy
▫ FESS
▫ Maxillary antral irrigation
▫ Balloon sinuplasty

45. Systemic antibiotics
• Controversial- lack of evidence
• should use for acute exacerbation
• First-line: broad spectum such as Amoxicillin-clavulanic acid
• If MRSA suspected: combine Clindamycin, TMP-SMZ
• Cystic fibrosis: Fluoroquinone (cover Pseudomonas)
• Macrolide: anti-inflammatory effect
CRS in children: what a the treatment options? Immunol Allergy Clin N Am 2009
CRS : epidermiology and medical management. JACI 2011

46. Systemic antibiotics
CRSsNP
• Short-term (<4 wk)
▫ cefaclor/amoxicillin improve in
RARS (56%)
▫ Amoxicillin-clavulanic 67% vs
ciprofloxacin 83% (cure rate, 9
days)
• Prolong course
▫ Open label adult study-
clindamycin/amox-clav/
doxycycline 6 wk: improve CT at 3,
6 wk
CRSwNP
• S aureus colonization 64%
▫ Doxycycline for 20 days –
smaller polyps, secretion
▫ Doxycycline –small effect on size
at 12 wk (quinolone, amox-clav
not)
Oral steroids and doxycycline: approaches to treat nasal polyps. JACI 2010
Short-term ATB in nasal polyps and S aureus. Eur Arch Otorhinolaryngol2009
Cefaclor vs amoxicillin in the treatment of sinusitis. Arch Fam Med. 1993
Radiographic resolution of CRS after oral antibiotics. Ann AlAsthma Imm2007

47. Long term systemic Macrolide
• Anti inflammatory effect in addition to bacteriostatic
• Erythromycin 500 mg/d 2 wk then 250 mg/d 10 wk combine
with nasal irrigation and INCS – improve
• Roxithromycin 150mg/d 12 wk – change from baseline at 12 wk
• Azithromycin 500 mg/d 3 d then 200mg/wk 11 wk - no
significant
Evaluation of the medical and surgical treatment of CRS . Laryngoscope. 2004.
A dbRCT of macrolide in the treatment of CRS. Laryngoscope. 2006
Lack of efficacy of long-term, low-dose azithromycin in CRS. Allergy 2011

48. Systemic antibiotics in children
• Available data does not justify the use of short-term oral
antibiotics for the treatment of CRS in children (Strength of
recommendation: B)
• There might a place for longer-term antibiotics (equivalent to CRS
in adults) (Strength of recommendation: D)
• Combination ATB+INCS, no specific recommendation for duration
• Short-term show inadequate to relieve symptoms, long –term 3-6
weeks most recommend
European position paper on Rhinosinusitis and nasal polyp 2012
CRS in children: what are the treatment option. Imm Allergy Clin N Am 2009

49. Systemic antibiotics in children
• Lack of good evidence, often treat with same ATB for ARS
• Type often depends on local resistance patterns
• IV antibiotics- lack of RCT, other intenvention
▫ Retrospective study (Don et al) -89% resolution after maxillary sinus
irrigation and adenoidectomy followed by IV ATB 1-4 wk
(Cefuroxime>Sulbactam>Ticarcillin clavulanate>Vancomycin)
Diagnosis and management of Rhinosinusitis, a practice parameter update.2014

50. Topical antibiotics
• Systematic review -antibiotic nasal irrigations or nebulizations
• Both CRS and acute exacerbations of CRS might benefit
• Use 3 to 6 weeks
• Topical irrigation with 80 mg/L gentamicin or tobramycin can
also be useful
• Caution: SNHL 23% in CF +frequent irrigations with
aminoglycosides
Topical antimicrobials in the management of CRS: a systematic review. Am J Rhinol 2008
CRS : epidermiology and medical management. JACI 2011

51. Intranasal steroids
• Helpful in all types of CRS
• no RCT in children, recent study show modest benefit
• suppress mucosal inflammation especially co-morbid with AR,
asthma
• CRS can exacerbate asthma INCS reduce
• duration coincide with the longer use of antibiotics typically
3-6 wk
• Mometasone fuorate 2 yr, Fluticasone propionate 4 yr
CRS in children: what are the treatment option. Imm Allergy Clin N Am 2009
CRS in children. Pediatr Clin N Am 2013

52. Systemic steroid
• A brief course of oral glucocorticoids - treatment for NP (‘medical
polypectomy'), AFRS
• Children
▫ additional effect on cough, CT scan, nasal obstruction
▫ consider when INCS fail to relieve mucosal inflammation
• Hamilos. JACI 2011
▫ prednisone 20 mg bid x 5 d10 mg bid x5 d 10 mg od x 5 d TCS
• British guidelines
▫ prednisolone 0.5 mg/kg for 5-10 days + betamethasone nasal drops
• Hissaria, JACI2006(Adult trial)
▫ prednisone 30 mg od x 4 d with 5 mg↓ q2days IN budesonide 400 mg bid
CRS Epidemiology and medical management. JACI 2011
CRS in children: what are the treatment option. Imm Allergy Clin N Am 2009

53. Systemic steroid in children
• No RCT in children
• Amoxicillin/clavulanate for 30 days and randomized to
receive methylprednisolone or placebo, average age 8 yr
▫ 1 Mkday for 10 days, 0.75 MKday for 2 days, 0.5 MKday for
2 days, 0.25 MKday for 1 day
• CT score +symptom - significant improvements both ATB
alone and ATB+ steroids
Efficacy and tolerability of systemic methylprednisolone in children and adolescents with
CRS: dbRCT. JACI2011

54. Topical steroid irrigations
• Aqueous budesonide 5-mg respule + 1 tsp of saline- benefit in CRS
▫ head down forward-->right lateral supine-->supine position, 1-2
min once daily
• Fluticasone propionate 200 mg per nostril - benefit in polyp
▫ Position: lie on backs with heads hanging down in an inverted
vertical position, 2 min, once daily
• reduced the need for surgery, improved hyposmia, and decreased
nasal polyp volume
CRS : epidermiology and medical management. JACI 2011

55. • Objective=evaluate the efficacy of postoperative
topical sinonasal steroid irrigations for CRS
▫ budesonide (1 mg) or betamethasone (1 mg) in 240 mL
of normal saline solution
• Improve SNOT-22 score, esp high tissue eosinophilia
(>10/hpf)

56. Nasal saline and nasal spray
• Adjunctive
• saline irrigation and sprays (1-4 times/day) -effective
• less effective as monotherapy compared to topical steroid
• Effect: reduces postnasal drainage, removes secretions, rinses
away allergens and irritants, and improves mucociliary
clearance
• Nasal larvage (at least 200 mL of warmed saline) with squeeze
bottles, syringes, and pot
Nasal saline irrigations for the symp-toms of chronic rhinosinusitis.
Cochrane Database Syst Rev 2007

57. Adjunctive therapy
• Antihistamine
• Decongestant
• Mucolytic agents
• Antileukotriene
▫ Adjunct to topical glucocorticoids in the treatment of CRSwNP
▫ more effective in those with concomitant asthma and aspirin
intolerance (AERD)
• Antireflux therapy
CRS Epidemiology and medical management. JACI 2011
CRS in children. Pediatr Clin N Am 2013

58. Antifungal
• Based on "fungal hypothesis"
• Studies showed (1) fungal hyphae colonize in patients with
CRS (2) CRS show a systemic immune hyperresponsiveness to
common inhalant fungi, such as Alternaria species
• However, neither topical antifungals (sprays and irrigations)
nor systemic terbinafine are beneficial
Diagnosis and management of Rhinosinusitis, a practice parameter update.2014
CRS Epidemiology and medical management. JACI 2011

59. CRS Epidemiology and medical management. JACI 2011

60. CRSsNP
• Intensive medical therapy: a brief course of systemic
glucocorticoids + a prolonged course of oral antibiotics + 1 or
more adjunctive therapies
• Typical regimen: oral prednisone 20 mg bid for 5 days 20 mg
od for 5 days plus 3 -4 weeks of oral ATB (Amoxicillin-clavulanate
is an excellent choice for most), sinus culture
• extend up to 6 weeks in patients with colored secretion
• Maintenance: TCS, considers long-term macrolide
CRS Epidemiology and medical management. JACI 2011

61. CRS Epidemiology and medical management. JACI 2011

62. CRSwNP -management
• Initial: brief course of oral glucocorticoids, TCS
• Maintenance:
▫ TCS
▫ Mucosal colonization with S aureus 64% CRSwNP (30%
healthy) –Doxycycline begin at week 2 and persist for 12
weeks
▫ Antileukotrienes and aspirin desensitization
▫ Surgery
CRS Epidemiology and medical management. JACI 2011

63. CRS Epidemiology and medical management. JACI 2011

64. AFRS- management
• Surgery
• Systemic steroid: 1 mg/kg prednisone for 10 days, slowly reduced
by 1 to 2.5 mg/wk post-op
• after surgery, topical glucocorticoid with budesonide
• oral or topical antifungal- no trials, some respond (200 mg twice-
daily oral itraconazole to adults for 3 to 6 months)
CRS Epidemiology and medical management. JACI 2011

65. Indication for surgery in CRS
1. Complete nasal obstruction in CF caused by massive
polyposis or medialization of the lateral nasal wall
2. Orbital abscess
3. Intracranial complications
4. Antrochoanal polyp
5. Mucocoeles or mucopyocoeles
6. Fungal rhinosinusitis
CRS Epidemiology and medical management. JACI 2011

66. Adenoidectomy
• Remove infection reservoir, biofilms
• Meta-analysis in children 9 studies, mean age 5.8 yr-8/9 show
improvement 69.3%
• One study (Ramadan) show asthma +young(<7yr) likely to
fail combine with FESS
CRS in children: what are the treatment option. Imm Allergy Clin N Am 2009
Diagnosis and management of Rhinosinusitis, a practice parameter update.2014

67. Maxillary antral irrigation
• Optimize benefit of adenoidectomy
• Clear seceretion/infection+ provide culture material
• Adenoidectomy alone 61% vs combine 88% (in 32
children with CRS)
• Post-op antibiotic- no improvement, not necessary
Diagnosis and management of Rhinosinusitis, a practice parameter update.2014
CRS in children: what are the treatment option. Imm Allergy Clin N Am 2009

68. Functional endoscopic sinus surgery
(FESS)
• When adenoidectomy fail-stepwise approach
• Mucociliary clearance disorder such as CF, Kartagener
syndrome- offer first option
• In children, less widespread due to concerns of hindering
midface growth
• Outcomes are excellent 80-100% improve
• Second-look: majority not endorsed
• Risk (meta-analysis -0.6%) globe, CSF leak, nasolacrimal duct
injury
CRS in children: what are the treatment option. Imm Allergy Clin N Am 2009

69. • Many advocate a conservative approach to FESS in
children, limited to removal of any obvious
obstruction (such as polyps and concha bullosa), as
well as anterior bulla ethmoidectomy and maxillary
antrostomy

70. Balloon catheter sinuplasty (BCS)
• Ballon dilatation of sinus ostia
• Alternative to FESS
• primarily used for maxillary sinus
CRS in children. Pediatr Clin N Am 2013

71. Thank you