4. Hospital Course
• 응급실
– 벤톨린 네뷸라이저, 산소 공급
– 경구용 스테로이드 1회 투여
– 4시간 후에도 호전 없이, 증상 악화
• 중환자실
– 입원 후 Solu-Medrol 투여하였으나, 빈호흡과 호흡곤란이
악화되어 중환자실로 전실
– 6시간 간격으로 Solu-Medrol, 속효성 기관지 확장제 투여
– 3일 후 호전되어 병실로 전실 후 5일째 퇴원
• 집
– 풀미코트 1일 2회 투여
– 담배 피는 할아버지에 대한 교육 시행
5. 천식 악화 원인으로 생각되는 것은?
1. RSV(respiratory syncytial virus)
2. Streptococcus pneumonia
3. Influenza
4. hRV(human rhinovirus)
6. RT-PCR of Nasal Swab
• RSV A and B : negative
• Influenza A and B : negative
• Human Rhinovirus(hRV) : positive
7. What infection during infancy is
most associated with the
subsequent development of
childhood asthma?
8. Which of the following appears to be
associated with asthma?
A) Influenza
B) HRV (human rhinovirus)
C) hMPV (human metapneumovirus)
D) Chlamydia pneumonia
E) All of the above
9. 천식과 호흡기 바이러스 감염
Viral
infection
• Recurrent wheeze,
• Incident asthma
Young children
• Exacerbation,
• Decreased lung
function
Present asthma
10. 호흡기의 발달- 태내발달
0 4 6 16 26 32week
• 배아기(Embryonic period, 임신 4-6주)
• 가선기(Pseudoglandular period, 임신 6-16주)
• 세관지(Canalicular period, 임신 16-26주)
• 소낭기(Saccular period, 임신 26-32주)
• 폐포기(Alveolar period, 임신 32주- 출생)
11. 호흡기의 발달- 출생 후 성장
• 폐, 기관지의 발달
– 출생에서 18개월까지
• 2세까지는 폐포의 수가 증가하며
• 호흡 세기관지(bronchiole)와 폐포관(alveolar duct)그리고 폐포의 기능이 성
숙한다.
13. A. B.
그림 2. 호흡기의 출생 후 성장
C.
A. B. 18개월까지는 폐포의 수가 증가하며 호흡 세
기관지(bronchiole)와 폐포관(alveolar duct)과 폐포
의 기능이 성숙한다.
C. 18개월 이후에는 폐포 수의 증가는 현저히 감소하
고, 호흡기의 전반적인 크기가 증가한다. 이 시기 기
관지 연골도 4세까지 지속적으로 단단해 진다.
14. 호흡기 방어기능의 발달
• 방어 체계의 발달
– 점막
• 1차 방어선
– 호흡기 상피를 따라 발달한 면역계
• 2, 3차 방어선
1. 면역계의 발달이 미숙한 영유아에서는 1차 방어선인 점막의 역할이 중요하므로
2. 적절한 습도를 유지하고, 물리적 손상을 막아서 점막 기능을 극대화 시켜야 한다.
감염 예방을 위해 가족들의 위생 관리가 철저해야 하고, 사람이 많은 곳에 가는 것을
제한하며
3. 분비형 IgA가 점막 방어기전에 중요인자 이므로 IgA가 풍부한 모유 수유가 중요하
다.
15. • 물리적 방어 기전: 1차, 2차 방어선
– 가온, 가습
• 비강은 표면적이 넓고, 혈관과 섬모 상피세포가 많아 흡입한 공기에
효과적으로 온도와 습도를 높여준다.
• 신생아와 영아의 호흡은 비강호흡에 많이 의존한다.
– 미립자의 제거
• 비강 내에서는 코털에서
• 기관지로 들어온 것은 기관지 점액막층(mucus blanket)에 부착되어
섬모운동에 의해서 제거된다.
16. 공기
온도 29-32도, 상대습도 95%
온도 32-34도
상대습도 100%
온도 37도
상대습도 100%
25. Vitamin D deficiency and incidence of
viral infection
• “Rachitic Lung”: children with rickets have
more respiratory infections
– Lung abnormalities included: lobar atelectasis,
interstitial pneumonitis, pulmonary edema with
cardiomegaly
– Respiratory infections increased in children with
“sub-clinical rickets”
Khajavi and Amirhakimi Clin Ped 1977;16:1
Rehman J Trop Pediatr 1994;40:58
26. Rate of URTI varied by Vit. D level
Ginde et al. Arch Inern Med
2009;169:384
27. Season and Influenza A:
Do vitamin D levels play a role?
Review by Cannell et al. Epidemiol Infect
2006;134:1129
28. What is the level of proof that vitamin D
sufficiency would be protective?
• Increased rate of respiratory infectins in non-rachitic children
with vit D deficiency returned to control levels after 6 weeks
of high dose vit D
• RCT in 334 school children in Japan
– Intervention group: 1200 IU/d, control 200 IU/d
– Outcome of Inf. A infection
• Intervention 18/167, 10.8%
• Placebo 31/167, 18.6%
• RR of 0.36 (p=0.006)
Rehman J Tropical Pediatrics 1994
Urashima et al. Am J Clin Nutr 2010;91:1255
29. What is the level of proof that vitamin D
sufficiency would be protective?
• Secondary outcome of a trial for bone loss
– Women in intervention group (2,000 IU/d) had fewer respiratory
infections than in control group: 7.7% vs. 25.0%
Aloia and Li-Ng Correspondence to Epidemiol Infect 2007;135:1095
30. Mechanisms by which vitamin D
decreases viral infection
• Limits production of pro-inflammatory cytokines,
suppressing inflammation
• Increases factors that inactivate viral pathogens: e.g.,
cathelicidin, beta-defensin
• Primary airway epithelium generate active D that
decreases inflammatory response to viral infection
• Enhances T regulatory cell suppression
Hansdorrir et al. J Immunol 2008;181:7090
Hansdorrir et al. J Immunol 2010;184:965
31. Vitamin D levels and incidence of
viral infection in young children
• Cord-blood levels associated with resp infection
– Lower levels associated with higher risk of resp infection
by 3 months of age after adjusting for season of birth
2.5
2
1.5
respiratory infection
any infection OR
1
0.5
0
>75 25-74 <25
25(OH)D concentration, nmol/L
Camargo et al.
Pediatrics
2011;127:e180
32. Vitamin D levels and incidence of
viral infection in young children
• Cord-blood levels associated with resp infection
• Low levels associated with increased probability of a
viral co-infection (more than 1 concurrent viral
infection
Most notable for RSV
and RV
Deficient
Camargo et al.
JACI 2010;126:1074
33. Are vitamin D levels associated with severity
of viral infections in young children?
• Pro
– Case control study of 15 newborns with LRTI admitted to
NICU
• 15 healthy controls matched for GA, birth weight, age, gender
• Levels in LRTI group 9 + 9 vs. controls 16 + 13, p=0.012
• Plus/minus
– Deficiency noted in bronchiolitis only in those admitted to
ICU, not to general pediatric ward vs. well controls
• Con
– Maternal D evel not assciated with infant bronchiolitis
score
Karatekin et al. Eur J Clin Nutrution 2009;63:473
McNally et al. Ped Pulm 2009;44:981
Carroll et al. AJOG 2011;215:e1
34. Vitamin D deficiency and
viral infection-induced exacerbations
• Higher levels associated with decrease
markers of allergy and asthma severity
0.25
0.2
0.15
0.1
0.05
0
ICS or LM ICS or LM PD20 Hosp
OR
Brehm et al. AJRCCM 2009;179:765
P=0.20
P=0.004 P=0.05
P=0.03
35. Vitamin D deficiency and viral
infection-induced exacerbations
• Lower levels associated with increase markers
of allergy and asthma severity
• Insufficient levels associated with risk of
severe exacerbation, particularly when not on
ICS
37. Risk of exacerbation over 4 years
increased by a combination of ICS use
and vit D status
Exacerbation No Yes Percentage OR (95% CI)
ICS, D suff 162 52 24 1.0 (reference)
ICS, D insuff 58 31 35 1.7 (1.0-2.9)
No ICS, D suff 289 158 35 1.7 (1.2-2.5)
No ICS, D insuff 166 105 39 2.0 (1.3-2.0)
Brehm et al. JACI 2010;126:52
38. Conclusions
• Viral infections play a prominent role in:
– Affecting asthma incidence in young children
• Prominent role of rhinovirus
– Precipitating asthma exacerbations
– Leading to loss of lung function
• Vitamin D deficiency associated with:
– Increased rate of infections overall, particularly viral respiratory and in
young children
– Increased pro-inflammatory cytokines and decreased factors for viral
inactivation on airway epithelium
– Increased markers of allergy and asthma severity, and exacerbations
• Need for RCTs to document improvement in outcomes with
vit D supplementation
39. Questions
• Evidence for viral infections:
–Affecting asthma incidence in young
children
• Prominent role of rhinovirus
–Precipitating asthma exacerbations
–Leading to loss of lung function
40. Viral infection and asthma
incidence
• RSV bronchiolitis liked to development of wheeze
and asthma at age 5 years
– Related to episode severity
– Interaction with family history of asthma
• Rhinovirus (RV) plays a role more important than RSV
– OR for development of asthma
• 2.6 for RSV
• 9.8 for RV
– Improvement in detection via molecular techniques
allowed determination of role for RV
41. RSV bronchiolitis and asthma
outcome: Role of family history
Sigurs et al. Thorax 2010; 65:1045
42. Role of viral infection early in life on asthma
development
Risk of asthma at age 6 years
in children who wheezed
during the first 3 years of life
with rhinovirus (RV),
respiratory syncytial
virus (RSV), or both
(*P , 0.05 vs. Neither;
+P , 0.05 vs. RSV only).
OR = odds ratio.
Jackson et al. AJRCCM 2008;178:667
43. Viruses that exacerbate asthma by year of age,
by asthma outcome
RV – rhinovirus
RSV – resp syn virus
PIV – para influenza virus
Flu – influenza A and B
CV – coronovirus
MPV – metapneumo virus
AdV – adenovirus
EnV – enterovirus
Jackson et al. AJRCCM 2008;178:667
44. Viruses Trigger Most Asthma
Exacerbations in Children
• Viruses were detected in:
– 80% of reported episodes of reduced peak
expiratory flow
– 80% of reported episodes of wheeze
– 85% of reported episodes of upper respiratory
symptoms, cough, wheeze, and a fall in peak
expiratory flow
Johnson SL et al. BMJ 1995;310:1225
45. Viral Detection During 292
Respiratory Episodes
160
140
120
100
80
60
40
20
0
Picornavirus
Coronavirus
Influenza
Parainfluenza
RSV
Other
No virus
Number of episodes
Picornavirus = Rhinovirus or enterovirus
Johnson et al. BMJ 1995;310:1225
46. Viral infection and decrease in lung
function
• Severe exacerbations (severe asthma-related
event, SARE) are associated with decline in
lung function
– Protective effect of regular ICS use
O’Byrne et al. AJRCCM 2009;179:18
47. Viral infection and decrease in lung
function
• Severe exacerbations are associated with
decline in lung function
• Decreased lung function after preschool
wheezing RV, but not RSV, illnesses
Guilbert et al. JACI 2011;128:532
61. The Journal of Pediatrics, Volume 156, Issue 5, May 2010, Page A3
Robert W. Wilmott
62.
63. The recent evidences indicate that
montelukast may reduce the
frequency of post-bronchiolitic
wheezing without causing significant side
effects but that it has no effects on decreasing incidences
of recurrent wheezing, symptom-free days, or the associated
usage of corticosteroid in post-bronchiolitis patients.
The small number of enrolled participants and the inability to pool all clinical outcomes precludes us from making solid
recommendations.
65. 결 론
나한테 그런 것은
물어보지 마세요.
오늘의 강의는
천식이 호흡기 바이러스 감
염과 밀접한 관계가 있다는
것입니다.
66. 정리해보면…
• 호흡기 바이러스 감염의 빈도는 혈중 Vit-
D 레벨이 낮은 것과 관련이 있다.
• 호흡기 바이러스 감염 원인 중 hRV가 천식
의 유발과 악화에 더 큰 역할을 한다.
• 특히 어릴 때 hRV로 인해 폐기능이 저하되
면 평생 영향을 미친다.
• 몬테루카스는 세기관지염 후 wheezing의
빈도를 낮출 수 있다.
67. 약간 의문이 드는 것
• 비타민 D를 계속 먹이면 호흡기 바이러스
감염 예방에 도움을 줄 가능성이 있다.
• 그러나 그 용량을 얼마나 주어야 할 것인
지에 대한 연구가 필요하다.
• 어린이들의 야외활동 시간을 늘려주면, 감
기에 덜 걸릴 가능성이 있지 않을까?하는
생각을 할 수도 있지만, 질병 관리 본부의
감기 예방 수칙에는 아직 그런 것은 없다.
68. 제목: Greeting Man
작가: 유영호
설치: 파주 헤이리
제가 아는 것을 홀딱 벗고
다 알려 드렸습니다. 경청해
주셔서 감사합니다.