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What 2012 pulmonology
1. WHAT YOU SHOULD HAVE READ BUT….2012
pulmonology
Attilio Boner
University of
Verona, Italy
2. Cord Blood Vitamin D Deficiency Is Associated With
Respiratory Syncytial Virus Bronchiolitis
Belderbos Pediatrics 2011;127:e1513
156 healthy term Cord blood concentrations of 25-OHD in
neonates. neonates who subsequently developed RSV
LRTI (n=18) and those who did not (n=138)
25-hydroxyvitamin D
(25-OHD) in cord blood
plasma.
Lower respiratory tract
infection (LRTI) caused
by Respiratory Syncytial
Virus (RSV) in the first
year of life, defined as
LRTI symptoms and
presence of RSV RNA in
a nose-throat specimen.
3. Cord Blood Vitamin D Deficiency Is Associated With
Respiratory Syncytial Virus Bronchiolitis
Belderbos Pediatrics 2011;127:e1513
156 healthy term Risk of RSV LRTI per quartile
of 25-OHD levels.
neonates. Because of the limited number of cases, the lower quartiles
(25 nmol/L, n=7; and 25–49 nmol/L, n=29) were pooled
25-hydroxyvitamin D
(25-OHD) in cord blood
plasma.
Lower respiratory tract
infection (LRTI) caused
by Respiratory Syncytial
Virus (RSV) in the first
year of life, defined as
LRTI symptoms and
presence of RSV RNA in
a nose-throat specimen.
4. Cord Blood Vitamin D Deficiency Is Associated With
Respiratory Syncytial Virus Bronchiolitis
Belderbos Pediatrics 2011;127:e1513
156 healthy term Risk of RSV LRTI per quartile
of 25-OHD levels.
neonates. Because of the limited number of cases, the lower quartiles
Vitamin D (25 nmol/L, n=7; and 25–49 nmol/L, n=29) were pooled
25-hydroxyvitamin D
deficiency in
(25-OHD) in cord blood
healthy neonates is
plasma.
associated with
Lower respiratory tract
increased risk of
infection (LRTI) caused
RSV LRTI in the
by Respiratory Syncytial
Virus (RSV) in year
first the first
of life.
year of life, defined as
LRTI symptoms and
presence of RSV RNA in
a nose-throat specimen.
5. Cord Blood Vitamin D Deficiency Is Associated With
Respiratory Syncytial Virus Bronchiolitis
Belderbos Pediatrics 2011;127:e1513
156 healthy term Risk of RSV LRTI per quartile
of 25-OHD levels.
neonates. Because of the limited number of cases, the lower quartiles
Intensified (25 nmol/L, n=7; and 25–49 nmol/L, n=29) were pooled
25-hydroxyvitamin D D
routine vitamin
(25-OHD) in cord blood
supplementation
plasma.
during pregnancy
may be a useful
Lower respiratory tract
infection (LRTI) caused
strategy to prevent
by Respiratory Syncytial
RSV LRTI
Virus (RSV) in the first
year during defined as
of life, infancy.
LRTI symptoms and
presence of RSV RNA in
a nose-throat specimen.
6. Lung function prior to viral lower respiratory tract
infections in prematurely born infants
Drysdale Thorax 2011;66:468
Objective
Prematurely born infants who develop respiratory syncytial virus
(RSV) lower respiratory tract infections (LRTIs) have lung
function abnormalities at follow-up.
The aim of this study was to determine whether prematurely born
infants who developed symptomatic RSV, or other viral LRTI(s),
had poorer premorbid lung function than infants who did not
develop LRTIs during the RSV season.
?
7. Lung function prior to viral lower respiratory tract
infections in prematurely born infants
Drysdale Thorax 2011;66:468
Functional residual capacity (FRC),
compliance (Crs) and resistance (Rrs)
of the respiratory system measured
% infants developing LRTs
at 36 weeks postmenstrual age.
50 –
Nasopharyngeal aspirates whenever
the infants had an LRTI.
RSV A and RSV B, rhinovirus,
40 – 46%
influenza A and B, 30 – 73/159
parainfluenza 1, 2 and 3,
human metapneumovirus and
20 –
adenovirus.
159 infants with a median gestational 10 –
age of 34 (range 23-36) weeks
prospectively followed.
0
8. Lung function prior to viral lower respiratory tract
infections in prematurely born infants
Drysdale Thorax 2011;66:468
Functional residual capacity (FRC),
compliance (Crs) and resistance (Rrs)
of the respiratory system measured Overall, there were
at 36 weeks postmenstrual age. no significant differences
Nasopharyngeal aspirates whenever in the FRC (p=0.54),
the infants had an LRTI. Crs (p=0.11) or
RSV A and RSV B, rhinovirus, Rrs (p=0.12) results
influenza A and B, between those who
parainfluenza 1, 2 and 3, developed an RSV
human metapneumovirus and or other viral LRTI
adenovirus.
and those who did not
159 infants with a median gestational develop an LRTI.
age of 34 (range 23-36) weeks
prospectively followed.
…but…
9. Lung function prior to viral lower respiratory tract
infections in prematurely born infants
Drysdale Thorax 2011;66:468
Functional residual capacity (FRC),
compliance (Crs) and resistance (Rrs)
of the respiratory system measured
at 36 weeks postmenstrual age. Infants with RSV
or other viral LRTIs
Nasopharyngeal aspirates whenever
the infants had an LRTI. who were admitted to
hospital compared
RSV A and RSV B, rhinovirus, with those who
influenza A and B,
parainfluenza 1, 2 and 3, were not had higher
human metapneumovirus and Rrs results (p=0.033 and
adenovirus. p=0.039, respectively).
159 infants with a median gestational
age of 34 (range 23-36) weeks
prospectively followed.
10. Lung function prior to viral lower respiratory tract
infections in prematurely born infants
Drysdale Thorax 2011;66:468
Functional residual capacity (FRC),
compliance (Crs) and resistance (Rrs)
Diminished
of the respiratory system measured
at 36premorbid lung
weeks postmenstrual age. Infants with RSV
or other viral LRTIs
function
Nasopharyngeal aspirates whenever
who were admitted to
the infants had an LRTI.
may predispose hospital compared
RSV A and RSV B, rhinovirus,
prematurely born
influenza A and B,
with those who
parainfluenza 1, to severe were not had higher
infants 2 and 3, and
human metapneumovirus Rrs results (p=0.033 and
adenovirus. LRTIs in
viral p=0.039, respectively).
infancy.
159 infants with a median gestational
age of 34 (range 23-36) weeks
prospectively followed.
11. Viral-mediated Inhibition of Antioxidant Enzymes
Contributes to the Pathogenesis of Severe Respiratory
Syncytial Virus Bronchiolitis Hosakote AJRCCM 2012;183:1550
Rationale
Respiratory syncytial virus (RSV) is a major cause of lower respiratory
tract infections in children, for which no specific treatment or vaccine
is currently available.
We have previously shown that RSV induces reactive oxygen species in
cultured cells and oxidative injury in the lungs of experimentally
infected mice. The mechanism(s) of RSV-induced oxidative stress in
vivo is not known.
Objectives
To measure changes of lung antioxidant enzymes expression/activity
and activation of NF-E2-related factor 2 (Nrf2), a transcription factor
that regulates detoxifying and antioxidant enzyme gene expression, in
mice and in infants with naturally acquired RSV infection.
12. Viral-mediated Inhibition of Antioxidant Enzymes
Contributes to the Pathogenesis of Severe Respiratory
Syncytial Virus Bronchiolitis Hosakote AJRCCM 2012;183:1550
Superoxide dismutase 1 (SOD 1),
SOD 2, SOD 3, catalase,
glutathione peroxidase, and
glutathione S-transferase, RSV infection induced a
as well as NF-E2-related factor significant decrease in the
2 (Nrf2 )expression,
expression and/or activity
were measured in murine
bronchoalveolar lavage, cell of SOD, catalase,
extracts of conductive airways, Glutathione S-transferase,
and/or inhumannasopharyngeal and glutathione peroxidase
secretions. in murine lungs and in the
Antioxidant enzyme activity and airways of children with
markers of oxidative cell injury severe bronchiolitis.
were measured in either murine
bronchoalveolar lavage or
nasopharyngeal secretions.
13. Viral-mediated Inhibition of Antioxidant Enzymes
Contributes to the Pathogenesis of Severe Respiratory
Syncytial Virus Bronchiolitis Hosakote AJRCCM 2012;183:1550
Superoxide dismutase 1 (SOD 1),
SOD 2, SOD 3, catalase,
glutathione peroxidase, and
glutathione S-transferase, Markers of oxidative
as well as NF-E2-related factor
2 (Nrf2 )expression,
damage correlated with
were measured in murine severity of clinical illness
bronchoalveolar lavage, cell in RSV infected infants.
extracts of conductive airways, Nrf2 expression was also
and/or inhumannasopharyngeal significantly reduced in
secretions.
the lungs of viral-infected
Antioxidant enzyme activity and mice.
markers of oxidative cell injury
were measured in either murine
bronchoalveolar lavage or
nasopharyngeal secretions.
14. Viral-mediated Inhibition of Antioxidant Enzymes
Contributes to the Pathogenesis of Severe Respiratory
Syncytial Virus Bronchiolitis Hosakote AJRCCM 2012;183:1550
Superoxide dismutase 1 (SOD 1),
RSV infection
SOD 2, SOD 3, catalase,
glutathione peroxidase, and
induces
glutathione S-transferase, Markers of oxidative
significant
as well as Nrf2 expression, damage correlated with
down-regulation
were measured in murine severity of clinical illness
bronchoalveolar lavage, cell in RSV infected infants.
of the airway
extracts of conductive airways,
Nrf2 expression was also
antioxidant
and/or inhumannasopharyngeal
secretions. significantly reduced in
system in vivo, the lungs of viral-infected
Antioxidant enzyme activity and
likely oxidative cell injury
markers of
resulting in mice.
lung oxidative
were measured in either murine
damage.
bronchoalveolar lavage or
nasopharyngeal secretions.
15. Viral-mediated Inhibition of Antioxidant Enzymes
Contributes to the Pathogenesis of Severe Respiratory
Syncytial Virus Bronchiolitis Hosakote AJRCCM 2012;183:1550
Superoxide dismutase 1 (SOD 1),
Modulation of
SOD 2, SOD 3, catalase,
oxidative stress
glutathione peroxidase, and
Markers of oxidative
glutathione S-transferase,
as may paveexpression,
well as Nrf2 the way damage correlated with
toward important
were measured in murine severity of clinical illness
bronchoalveolar lavage, cell
advances in the
extracts of conductive airways,
in RSV infected infants.
therapeutic
and/or inhumannasopharyngeal Nrf2 expression was also
significantly reduced in
approach of
secretions.
the lungs of viral-infected
RSV-induced
Antioxidant enzyme activity and
mice.
markers of oxidative cell injury
were measured in lung murine
acute either
disease.
bronchoalveolar lavage or
nasopharyngeal secretions.
16. Viral-mediated Inhibition of Antioxidant Enzymes
Contributes to the Pathogenesis of Severe Respiratory
Syncytial Virus Bronchiolitis Hosakote AJRCCM 2012;183:1550
Antioxidant
enzymes are
reduced in
bronchoalveolar
lavage (BAL) of
respiratory
syncytial virus
(RSV)-infected
mice.
17. Viral-mediated Inhibition of Antioxidant Enzymes
Contributes to the Pathogenesis of Severe Respiratory
Syncytial Virus Bronchiolitis Hosakote AJRCCM 2012;183:1550
Western blots were
performed using
antibodies against
superoxide dismutase
(SOD) 1, SOD 2, SOD 3,
catalase, and glutathione
S-transferase (GST)-mu.
The figure is
representative of
3 independent
experiments, each
experiment with 4 mice
per group at each time
point.
18. Viral-mediated Inhibition of Antioxidant Enzymes
Contributes to the Pathogenesis of Severe Respiratory
Syncytial Virus Bronchiolitis Hosakote AJRCCM 2012;183:1550
Superoxide dismutase (SOD) 1, SOD 2, and SOD 3 in conductive airway epithelial cells.
Proteins of conductive airway epithelial Densitometric analysis of
cells were obtained by lysis lavage from Western blot band intensities using
respiratory syncytial virus (RSV)-infected Alpha Ease software.
or control mice (Day 1 after infection) * p<0.05 ***p<0.001
and analyzed by Western blot.
19. Viral-mediated Inhibition of Antioxidant Enzymes
Contributes to the Pathogenesis of Severe Respiratory
Syncytial Virus Bronchiolitis Hosakote AJRCCM 2012;183:1550
Respiratory syncytial
virus (RSV) infection
inhibits antioxidant
enzyme activity in the
lung.
Total superoxide
dismutase (SOD),
catalase, glutathione
peroxidase (GPx), and
glutathione S-
transferase (GST)
activity in
bronchoalveolar lavage
of groups of mice that
were RSV infected or
sham inoculated.
*p<0.05; **p< 0.01 and ***p<0.001 relative to control mice.
20. Viral-mediated Inhibition of Antioxidant Enzymes
Contributes to the Pathogenesis of Severe Respiratory
Syncytial Virus Bronchiolitis Hosakote AJRCCM 2012;183:1550
Respiratory syncytial virus (RSV) infection is associated with decreased levels of
nuclear Nrf2 in the lung 12 and 24 hours after infection with RSV
*p<0.05; **p<0.01 relative to control mice.
21. Viral-mediated Inhibition of Antioxidant Enzymes
Contributes to the Pathogenesis of Severe Respiratory
Syncytial Virus Bronchiolitis Hosakote AJRCCM 2012;183:1550
Concentrations of the oxidative stress markers in nasopharyngeal secretions (NPS) of
infants with naturally acquired respiratory syncytial virus (RSV) infections.
F2-isoprostane concentration Malondialdehyde concentration
**p < 0.01 and ***p < 0.001 compared with upper respiratory tract infection
22. Viral-mediated Inhibition of Antioxidant Enzymes
Contributes to the Pathogenesis of Severe Respiratory
Syncytial Virus Bronchiolitis Hosakote AJRCCM 2012;183:1550
Antioxidant enzyme expression in nasopharyngeal secretions (NPS) of infants with naturally
acquired respiratory syncytial virus (RSV) infections.
23. Viral-mediated Inhibition of Antioxidant Enzymes
Contributes to the Pathogenesis of Severe Respiratory
Syncytial Virus Bronchiolitis Hosakote AJRCCM 2012;183:1550
Antioxidant enzyme expression in nasopharyngeal secretions (NPS) of infants with naturally
acquired respiratory syncytial virus (RSV) infections.
Western blot analysis of superoxide
dismutase (SOD) 1, SOD 2, and SOD 3,
catalase, and glutathione S-transferase
(GST)-mu in NPS of children with:
• upper respiratory tract infections (URTI),
• bronchiolitis (BR),
• bronchiolitis with hypoxia (BR 1 H), and
• patients on ventilatory support (VS).
b-actin was used as a control for protein
integrity and equal loading of the samples.
24. Viral-mediated Inhibition of Antioxidant Enzymes
Contributes to the Pathogenesis of Severe Respiratory
Syncytial Virus Bronchiolitis Hosakote AJRCCM 2012;183:1550
Conclusion
RSV infection induces a significant decrease in the expression of
most antioxidant enzyme involved in maintaining cellular
oxidant–antioxidant balance in mice and children.
The exception is SOD 2, for which levels are reduced in the BAL
of infected mice but not in epithelial cell proteins of the conductive
airways or in nasopharyngeal secretions of infected children,
suggesting that airway epithelial cells may not be the only cellular
source of the lung antioxidant response measured in BAL of mice.
Other tissue resident cells, such as alveolar macrophages, which
are early targets of RSV infection, could contribute to the
observed BAL findings.
25. Rhinovirus-induced bronchiolitis and asthma development
Jartti Pediat Allergy Immunol 2011;22:350
The association between any sensitization The association between log10 number
and of sensitizations and
sole rhinovirus [human rhinovirus (HRV);n= 58], sole HRV,
sole respiratory syncytial virus [respiratory sole RSV,
syncytial virus (RSV); n = 35], sole EV,
sole enterovirus (EV; n = 34), sole HBoV,
sole human bocavirus (HBoV; n = 12), sole other virus (the only child was
sole other virus (n = 8), sensitized; not computable),
mixed virus (n = 87) and mixed virus, and
non-virus (n = 13) non-virus
associated wheezing in hospitalized children. associated wheezing in hospitalized
children.
26. Rhinovirus-induced bronchiolitis and asthma development
Jartti Pediat Allergy Immunol 2011;22:350
The association between any sensitization The association between log10 number
and of sensitizations and
sole rhinovirus [human rhinovirus (HRV);n= 58], sole HRV,
sole respiratory syncytial virus [respiratory sole RSV,
Low interferon responses have been
syncytial virus (RSV); n = 35], sole EV,
sole HBoV,
sole enterovirus (EV; associated with HRV bronchiolitis.
n = 34),
sole human bocavirus (HBoV; n = 12), sole other virus (the only child was
sole other virus (n = 8), sensitized; not computable),
mixed virus (n = 87) and mixed virus, and
non-virus (n = 13) non-virus
associated wheezing in hospitalized children. associated wheezing in hospitalized
children.
27. Rhinovirus-induced bronchiolitis and asthma development
Jartti Pediat Allergy Immunol 2011;22:350
The association between any sensitization The association between log10 number
and of sensitizations and
sole rhinovirus [human rhinovirus (HRV);n= 58], sole HRV,
Although recurrent wheezing is common after
sole respiratory syncytial virus [respiratory sole RSV,
syncytial virus (RSV);both RSV and HRV bronchiolitis, HRV
n = 35], sole EV,
sole enterovirus (EV; n = 34), sole HBoV,
bronchiolitis carries a markedly higher riskonly child was
sole other virus (the
of
sole human bocavirus (HBoV; n = 12),
persistent wheezing until 6 years of age and
sole other virus (n = 8), sensitized; not computable),
mixed virus (n = 87) and for childhood asthma. and
mixed virus,
non-virus (n = 13) non-virus
associated wheezing in hospitalized children. associated wheezing in hospitalized
children.
28. Rhinovirus-induced bronchiolitis and asthma development
Jartti Pediat Allergy Immunol 2011;22:350
Possible mechanisms of interactions between rhinovirus and allergy
in causing more severe asthma or asthma-like illnesses.
29. Rhinovirus bronchiolitis and recurrent wheezing:
1-year follow-up. Midulla F, Eur Respir J 2012;39:396
Rate of recurrent wheezing
60 -
313 infants
aged <12 months
50 –
52.7%
hospitalised for their p<0.001
40 –
first episode of
bronchiolitis. 30 –
14 respiratory viruses
assayed in nasal washings.
20 – 10.3%
10 –
Recurrent wheezing.
0
A 12-month follow-up. controls bronchiolitis
30. Rhinovirus bronchiolitis and recurrent wheezing:
1-year follow-up. Midulla F, Eur Respir J 2012;39:396
OR for recurrent wheezing
Recurrent wheezing. 4 –
A 12-month follow-up.
313 infants
3 – 3.3
aged <12 months 3.2
hospitalised for their 2 – 2.5
first episode of
bronchiolitis. 1 –
14 respiratory viruses
00
assayed in nasal washings. rhinovirus family history
infection for asthma
31. Preschool asthma after bronchiolitis in infancy
Koponen P, Eur Respir J 2012;39:76
% children with
current asthma at age 6.5
205 infants hospitalised
for bronchiolitis at 20 –
< 6 months of age.
Control visit at a
mean age of 6.5 yrs.
10 – 12.7%
Viral aetiology of
bronchiolitis,
on admission by
antigen detection. 0
32. Preschool asthma after bronchiolitis in infancy
Koponen P, Eur Respir J 2012;39:76
% children with current asthma according
to viral etiology of bronchiolitis
205 infants hospitalised 30 –
for bronchiolitis at
< 6 months of age.
20 – 24%
Control visit at a
mean age of 6.5 yrs. p=0.01
10 –
Viral aetiology of
bronchiolitis, 8.2%
on admission by
0
antigen detection.
RSV non-RSV
33. Preschool asthma after bronchiolitis in infancy
Koponen P, Eur Respir J 2012;39:76
% children with current asthma according
to viral etiology of bronchiolitis
The risk of asthma
205 infants hospitalised 30 –
forwas lower after
bronchiolitis at
< 6RSV bronchiolitis
months of age.
than after 20 – 24%
Control visit atcaused
bronchiolitis a
meanother viruses in
by age of 6.5 yrs. p=0.01
children hospitalised 10 –
Viral aetiology of age
at <6 months of
bronchiolitis, 8.2%
on admission by
0
antigen detection.
RSV non-RSV
34. Clinical Impact of RT-PCR for Pediatric Acute
Respiratory Infections: A Controlled Clinical Trial
Wishaupt Pediatrics 2011;128:e1113
Real-time polymerase chain reaction
(RT-PCR) testing is a quick sensitive
method for detecting respiratory
pathogens. There were no
Nasal wash specimens from patients significant differences
12 years of age with suspected between the groups
acute respiratory infections.
with respect to
The RT-PCR results were hospital admissions,
communicated to the clinicians
within 12 to 36 hours in the
length of hospital stay
intervention group and after 4 or duration of
weeks in the control group. antibiotic use.
583 patients: 298 in the
intervention group and
285 in the control group.
35. Clinical Impact of RT-PCR for Pediatric Acute
Respiratory Infections: A Controlled Clinical Trial
Wishaupt Pediatrics 2011;128:e1113
1. Although a positive viral diagnosis could be established for
many patients, the numbers of hospital admissions and the
lengths of hospital stays did not differ between the groups.
2. The need for hospitalization depends primarily on clinical
parameters, such as the degree of clinical illness,
the need for supplemental oxygen therapy, and
the need for bronchodilator nebulization therapy, rather
than a confirmed viral diagnosis.
36. Clinical Impact of RT-PCR for Pediatric Acute
Respiratory Infections: A Controlled Clinical Trial
Wishaupt Pediatrics 2011;128:e1113
3. The duration of antibiotic treatment was not significantly
influenced by RTPCR testing. This is partly explained
by physicians‘ concerns regarding bacterial superinfection
in patients with ARIs.
4. Unfortunately, positive RT-PCR results do not exclude the
possibility of bacterial superinfection; therefore, physicians
are unlikely to change the antibiotic treatment that has been
initiated. In addition, viral infection was reported previously
to predispose patients to bacterial superinfection.
In our study, the majority of patients with proven bacterial
pneumonia also had positive RT-PCR results for a virus.
37. Observational study of two oxygen saturation
targets for discharge in bronchiolitis
Cunningham, Arch Dis Child 2012;97:361
To assess the potential effect
of discharge oxygen saturation
(SpO2) ≥ 90% and ≥ 94% 1. Feeding problems
in bronchiolitis. resolved at
68 infants aged ≤ 18 mo a median of 11 h.
requiring therapeutic oxygen
for SpO2 ≤ 93%. 2. SpO2 became stable
for at least 4h at:
SpO2 assessed in air every 2 h. - 17 h for ≥ 90%
Time from admission - 63 h for ≥ 94%.
to re-establish feeding (>75% normal)
and for SpO2 to become stable
for 4h at ≥ 90% and ≥ 94%.
38. Observational study of two oxygen saturation
targets for discharge in bronchiolitis
Cunningham, Arch Dis Child 2012;97:361
Time difference (hours) Time to resolve feeding,
≥90% to ≥94% SpO2 in air for 4h. SpO2 ≥90% and ≥94% in air
in infants with bronchiolitis.
39. Observational study of two oxygen saturation
targets for discharge in bronchiolitis
Cunningham, Arch Dis Child 2012;97:361
Time difference (hours) Time to resolve feeding,
≥90% to ≥94% SpO2 in air for 4h. SpO2 ≥90% and ≥94% in air
in infants with bronchiolitis.
The median lag
between
stable oxygen
at ≥90% and ≥94%
for 3 observations
32
(≥4h) was 32h.
40. Observational study of two oxygen saturation
targets for discharge in bronchiolitis
Cunningham, Arch Dis Child 2012;97:361
Time difference (hours) Time to resolve feeding,
≥90% to ≥94% SpO2 in air for 4h. SpO2 ≥90% and ≥94% in air
in infants with bronchiolitis.
The time for all study
infants to achieve
a stable SpO2≥90%
and
resolve feeding
difficulties
was a median of 22h.
22
41. Observational study of two oxygen saturation
targets for discharge in bronchiolitis
Cunningham, Arch Dis Child 2012;97:361
1. This study identifies that stopping therapeutic oxygen
for acute recovering viral bronchiolitis at stable 90% SpO2
rather than 94% SpO2 could result in a median discharge
from hospital 22h earlier.
2. With an average length of stay of 3 days, this difference
represents a significant potential gain.
3. The clinical and safety effects of this policy have yet
to be assessed.
42. Clinical predictors of admission in infants with acute
bronchiolitis Marlais Arch Dis Child 2011;96:648
% infants admitted
449 infants
40 –
presenting with
acute bronchiolitis.
30 –
20 –
36%
10 –
0
43. Clinical predictors of admission in infants with acute
bronchiolitis Marlais Arch Dis Child 2011;96:648
% infants admitted
449 infants
40 –
presenting with
The 5 best predictors of
acute bronchiolitis.
30 – admission were:
1) age,
20 –
36% 2) respiratory rate,
3) heart rate,
10 –
4) oxigen saturations
5) duration of symtomps.
0
44. Clinical predictors of admission in infants with acute
bronchiolitis Marlais Arch Dis Child 2011;96:648
Bronchiolitis risk of admission score
45. Clinical predictors of admission in infants with acute
bronchiolitis Marlais Arch Dis Child 2011;96:648
Distribution of scores across admitted and
discharged children with sensitivity and
specificity at each score cut-off
46. Clinical predictors of admission in infants with acute
bronchiolitis Marlais Arch Dis Child 2011;96:648
Distribution of scores across admitted and
discharged children with sensitivity and
Scoring system couldcut-off
specificity at each score be a
useful addition to the safety
net scoring systems and be
employed effectively in the
emergency department,
particularly by inexperienced
clinicians.
47. Clinical predictors of admission in infants with acute
bronchiolitis Marlais Arch Dis Child 2011;96:648
Distribution of scores across admitted and
discharged children with sensitivity and
specificity at each score cut-off
The score is simple to use and takes
into account objective data.
A score of 3 or over could direct
the clinician to seek a review of the
child by a senior colleague before
allowing that child to be discharged.
48. Occult serious bacterial infection in infants younger than
60 to 90 days with bronchiolitis. A systematic review
Ralston APAM 2011;165:951
Rate of urinary tract
11 studies reporting infections
4 –
rates of serious
bacterial infection in
infants younger than
90 days with clinical
3 –
3.3%
bronchiolitis and/or 2 –
respiratory syncytial
virus infection.
1 –
0
49. Occult serious bacterial infection in infants younger than
60 to 90 days with bronchiolitis. A systematic review
Ralston APAM 2011;165:951
Bacteremia rates in infants with bronchiolitis or respiratory
syncytial virus infection.
50. Occult serious bacterial infection in infants younger than
60 to 90 days with bronchiolitis. A systematic review
Ralston APAM 2011;165:951
Bacteremia rates in infants with bronchiolitis or respiratory
syncytial virus infection.
No case of bacteremia was reported in 8 of 11 studies.
No case of meningitis was reported in any of the studies.
51. Occult serious bacterial infection in infants younger than
60 to 90 days with bronchiolitis. A systematic review
Ralston APAM 2011;165:951
Bacteremia rates in infants with bronchiolitis or respiratory
syncytial virus infection.
A screening approach to culturing for serious bacterial
infections in febrile infants presenting with bronchiolitis or
respiratory syncytial virus infection is very low yield.
52. Impact of PCR for respiratory viruses on antibiotic use:
Theory and Practice. van de Pol Pediatr Pulmonol 2011;46:428
Real-time polymerase chain reaction (PCR) for respiratory
viruses is more sensitive, yet more expensive, than
conventionally used direct immunofluorescence (DIF).
We determined the impact of real-time PCR, additional to
DIF, on antibiotic prescription in ventilated children with
lower respiratory tract infection (LRTI) at admission to
the pediatric intensive care unit (PICU).
The multicenter survey study (94 respondents) showed
that PCR decreased antibiotic use (P < 0.001).
53. Impact of PCR for respiratory viruses on antibiotic use:
Theory and Practice. van de Pol Pediatr Pulmonol 2011;46:428
In a prospective study,
children (≤5 years) with LRTI % children DIF (+)
tested at admission by DIF and
PCR. 50 –
Positive DIF results were 40 – 50%
reported at the end of the
first working day. 30 – 19/38
PICU physicians reported
20 –
antibiotic treatment on the
second working day. 10 –
After informing them of the
PCR result antibiotic treatment 00
was reevaluated.
54. Impact of PCR for respiratory viruses on antibiotic use:
Theory and Practice. van de Pol Pediatr Pulmonol 2011;46:428
In a prospective study,
children (≤5 years) with LRTI % children DIF (+)
testedthe admissionnegative and
Of at 19 DIF by DIF
PCR.patients 12 (63%) were 50 –
treated with antibiotics
Positive DIF results were
before revealing the PCR 40 – 50%
reported at the end of the
result; the PCR test was 19/38
first working day. 30 –
positive in 9 out of 12.
PICU physicians reporteddid
Revealing PCR results 20 –
antibioticalter antibiotic
not treatment on the
second working day.
treatment. 10 –
After informing them of the
PCR result antibiotic treatment 00
was reevaluated.
55. Impact of PCR for respiratory viruses on antibiotic use:
Theory and Practice. van de Pol Pediatr Pulmonol 2011;46:428
In a prospective study,
children (≤5 years) with LRTI % children DIF (+)
tested at admission by DIF and
In contrast to their
PCR.responses to the survey 50 –
Positive DIF real-life PICU
study, in results were
physicians did not let their
40 – 50%
reported at the end of the
first workingprescription be
antibiotic day. 30 – 19/38
influenced by respiratory
PICU physicians reported
20 –
antibiotic treatmentchildren
real-time PCR in on the
second working for LRTI.
ventilated day.
10 –
After informing them of the
PCR result antibiotic treatment 00
was reevaluated.
56. Impact of PCR for respiratory viruses on antibiotic use:
Theory and Practice. van de Pol Pediatr Pulmonol 2011;46:428
Flow chart of viral test results and antibiotic use of patients
enrolled in the prospective study
57. Unnecessary Care for Bronchiolitis Decreases With
Increasing Inpatient Prevalence of Bronchiolitis
Van Cleve Pediatrics 2011;128:e1106
1. Efforts to improve the quality of care for bronchiolitis have focused on
decreasing utilization through implementation of prespecified “pathways”
of care delivery: lack of utility of routine use of laboratory testing, steroids,
radiography, and antibiotics for patients with uncomplicated viral
bronchiolitis.
American Academy of Pediatrics, Subcommittee on Diagnosis and Management of Bronchiolitis.
Diagnosis and management of bronchiolitis. Pediatrics. 2006;118(4): 1774.
2. If high-quality care for bronchiolitis is defined in part on the basis of what
physicians choose not to do, why do patients continue to receive unnecessary
care?
58. Unnecessary Care for Bronchiolitis Decreases With
Increasing Inpatient Prevalence of Bronchiolitis
Van Cleve Pediatrics 2011;128:e1106
3. The clinical presentation of viral bronchiolitis includes fever, tachypnea,
and respiratory distress, all of which also can be symptoms of more-
serious bacterial illnesses.
4. Although diagnosis of a viral infection decreases the probability of other
illnesses, it does not exclude other causes of illness among infants.
5. To accept a clinical hypothesis that a patient has bronchiolitis
and to provide high-quality, evidence-based care, physicians must integrate
a patient‟s clinical presentation with contextual information that includes
the ―pretest‖ probability of illness.
59. Unnecessary Care for Bronchiolitis Decreases With
Increasing Inpatient Prevalence of Bronchiolitis
Van Cleve Pediatrics 2011;128:e1106
6. Failure to incorporate such information might lead to an inappropriately
low degree of faith in a clinical diagnosis, which might contribute to
overuse of diagnostic tests and empirical therapeutic measures.
7.In this study, we hypothesized that an important determinant of care
delivery to patients with eventual diagnoses of bronchiolitis would be the
inpatient bronchiolitis prevalence (IBP) in the hospital in which their care is
being delivered. A priori, we postulated that an elevated IBP would increase
physician/care team confidence that a patient‘s illness was caused by
bronchiolitis and therefore would decrease the likelihood that the patient
would receive care that is generally thought to provide little or no benefit
for bronchiolitis.
60. Unnecessary Care for Bronchiolitis Decreases With
Increasing Inpatient Prevalence of Bronchiolitis
Van Cleve Pediatrics 2011;128:e1106
During winter months,
with each 1% absolute
All patients increase in inpatient
2 months to 2 years
of age hospitalized bronchiolitis prevalence
with bronchiolitis (IBP), patients were less
during 2004–2008 likely to receive:
at pediatric hospitals. 1. steroids (P<0.001),
2. radiographs (P<0.001),
3. laboratory tests
(P<0.001).
61. Helium-Oxygen Therapy for Infants With Bronchiolitis
Kim APAM 2011;165:1115
Infants aged 2-12 months
with a Modified Wood‘s Mean change in M-WCAS
Clinical Asthma Score from baseline to 240 minutes.
(M-WCAS) of 3 or higher.
0
Randomized to the -0.31
helium-oxygen (n=34) -0.5 –
or oxygen (n=35) p<0.001
and received nebulized -1.0 –
racemic epinephrine via a -1.84
face mask. -2.0 –
Helium-oxygen Oxygen
group group
62. Helium-Oxygen Therapy for Infants With Bronchiolitis
Kim APAM 2011;165:1115
Infants aged 2-12 months
with a Modified Wood‘s
The mean M-WCAS was Mean change in M-WCAS
Clinical Asthma Score for
significantly improved from baseline to 240 minutes.
the helium-oxygen group
(M-WCAS) of 3 or higher.
compared with the 0
Randomized to the at
oxygen group -0.31
helium-oxygen (n=34)
60 minutes (p=0.005), -0.5 –
oxygen (n=35)
or120 minutes (p<0.001), p<0.001
and received nebulized
180 minutes (p<0.001), -1.0 –
racemic epinephrine via a
240 minutes (p<0.001). -1.84
face mask. -2.0 –
Helium-oxygen Oxygen
group group
63. Helium-Oxygen Therapy for Infants With Bronchiolitis
Kim APAM 2011;165:1115
Lowell Pediatrics 1987;79:939.
64. Helium-Oxygen Therapy for Infants With Bronchiolitis
Kim APAM 2011;165:1115
Mean Modified Wood‟s Clinical Asthma Scores
(M-WCASs) vs time.
65. Helium-Oxygen Therapy for Infants With Bronchiolitis
Kim APAM 2011;165:1115
Mean Respiratory Distress Assessment
Instrument (RDAI) scores vs time.
66. Helium-Oxygen Therapy for Infants With Bronchiolitis
Kim APAM 2011;165:1115
Nebulized racemic epinephrine delivered by
helium-oxygenRespiratory helium-oxygen inhalation therapy
Mean followed by Distress Assessment
Instrument (RDAI) scores vs time.
was associated with a greater degree of clinical improvement
compared with that delivered by oxygen among infants with
bronchiolitis.
67. Clinical predictors of nasal continuous positive airway
pressure requirement in acute bronchiolitis
Evans Pediatr Pulmonol 2012;47:381
1) Two to three percent of infants under 1 year of age are
admitted each year with bronchiolitis caused by RSV.
2) A small percentage of those admitted go on to require
ventilatory support.
3) There is an increasing awareness of the potential benefits
that non-invasive ventilation, such as nasal continuous positive
airway pressure (nCPAP) may confer over basic supportive
care in reducing the need for invasive ventilation in severely
affected infants.
68. Clinical predictors of nasal continuous positive airway
pressure requirement in acute bronchiolitis
Evans Pediatr Pulmonol 2012;47:381
To identify clinical % children requiring
factors in infants with nasal CPAP
20 –
acute bronchiolitis in the
emergency department
(ED), which might predict
15 –
17%
10 –
a requirement for nCPAP 28/163
following admission. 05 –
163 admitted infants. 00
69. Clinical predictors of nasal continuous positive airway
pressure requirement in acute bronchiolitis
Evans Pediatr Pulmonol 2012;47:381
Statistically Significant Predictors
% %
1Continuous variables presented as mean values and binary variables presented as percentages.
2Univariate binary logistic regression was used for statistical analysis and provides an odds ratio for a 1 point
change in the independent variable, i.e., odds ratio for a 1 point change in the unit of measurement for
continuous variable and odds ratio associated with the presence of a binary variable.
70. Increased protein-energy intake promotes anabolism
in critically ill infants with viral bronchiolitis:
a double-blind randomised controlled trial
de Betue Arch Dis Child 2011;96:817
Rates of protein kinetics (g/kg/24 h)
18 infants admitted to the
paediatric intensive care unit
in both study groups on day 5
with respiratory failure due
to viral bronchiolitis.
p<0.05
Continuous enteral feeding p<0.05
with protein and energy
enriched formula (PE-formula)
(n=8; 3.1±0.3 g protein/kg/24
h, 119±25 kcal/kg/24 h) or
standard formula (S-formula) p<0.05
(n=10; 1.7±0.2 g
protein/kg/24 h, Whole body Whole body Whole body
84±15 kcal/kg/24 h. protein protein protein
breackdown balance synthesis
71. Increased protein-energy intake promotes anabolism
in critically ill infants with viral bronchiolitis:
a double-blind randomised controlled trial
de Betue Arch Dis Child 2011;96:817
A positive
18 infants admitted to the
Rates of protein kinetics (g/kg/24 h)
Whole body
paediatric intensive care unit
in both study groups on day 5
protein balance
with respiratory failure due
to viral bronchiolitis.
was achieved p<0.05
in the
Continuous enteral feeding p<0.05
with protein and energy
PE-group,
enriched formula (PE-formula)
which was
(n=8; 3.1±0.3 g protein/kg/24
significantly
h, 119±25 kcal/kg/24 h) or
p<0.05
standard formula (S-formula)
higher than in
(n=10; 1.7±0.2 g
the S-group.
protein/kg/24 h, Whole body Whole body Whole body
84±15 kcal/kg/24 h. protein protein protein
breackdown balance synthesis
72. Increased protein-energy intake promotes anabolism
in critically ill infants with viral bronchiolitis:
a double-blind randomised controlled trial
de Betue Arch Dis Child 2011;96:817
Rates of protein kinetics (g/kg/24 h)
Increasing protein
18 infants admitted to the
in both study groups on day 5
and energy intakes
paediatric intensive care unit
with respiratory failure due
promotes protein
to viral bronchiolitis.
anabolism in
p<0.05
Continuous enteralill infants.
critically feeding p<0.05
Increased protein
with protein and energy
enriched formula (PE-formula)
and energy intakes
(n=8; 3.1±0.3 g protein/kg/24
should be preferred
h, 119±25 kcal/kg/24 h) or
above standard intakes
standard formula (S-formula) p<0.05
in these infants.
(n=10; 1.7±0.2 g
protein/kg/24 h, Whole body Whole body Whole body
84±15 kcal/kg/24 h. protein protein protein
breackdown balance synthesis
73. Discharged on Supplemental Oxygen From an
Emergency Department in Patients With Bronchiolitis
Halstead, Pediatrics 2012;129;e605
1) The primary reasons for admission include respiratory distress,
poor feeding, and hypoxia or the need for supplemental oxygen
(O2).
2) Practitioners are influenced by small changes in pulse-oximetry
data in the decision to admit patients with bronchiolitis.
3) With the increased use of pulse-oximetry, patients also remain
in the hospital for supplemental O2 for longer periods of time
after other parameters such as work of breathing and feeding
have returned to normal.
74. Discharged on Supplemental Oxygen From an
Emergency Department in Patients With Bronchiolitis
Halstead, Pediatrics 2012;129;e605
The American Academy of Pediatrics
1) The primary reasons for admission include respiratory distress,
poor feeding, and hypoxia or the need for be initiatedoxygen
recommends that O2 therapy supplemental
(O2). judiciously when O saturations 2
levels fall < 90% and that the intensity
2) Practitioners are influenced by small changes in pulse-oximetry
of monitoring O2 saturation levels
data in the decision to admit patients with bronchiolitis.
be reduced as the infant improves.
3) With the increased use of pulse-oximetry, patients also remain
in the hospital for of Pediatrics Subcommitteeof for longer periods of time
American Academy
supplemental O2onbronchiolitis. Pediatrics.
of Bronchiolitis; Diagnosis and management
Diagnosis and Management
after other parameters such as work of breathing and feeding
2006;118(4): 1774–1793
have returned to normal.
75. Discharged on Supplemental Oxygen From an
Emergency Department in Patients With Bronchiolitis
Halstead, Pediatrics 2012;129;e605
% patients
60 –
Retrospective chart review
of 4194 patients with 57%
bronchiolitis between 2005 40 –
and 2009.
Patients requiring baseline
20 – 28%
O2 were excluded.
Patients admitted after
15%
home O2 for adverse 0
on O2 room air admitted
outcomes. discharged
76. Discharged on Supplemental Oxygen From an
Emergency Department in Patients With Bronchiolitis
Halstead, Pediatrics 2012;129;e605
% patients
60 –
Retrospective chart review
of 4194 patients with on
Those discharged 57%
room air, 4% were
bronchiolitis between 2005 40 –
and 2009.
subsequently admitted,
and 6% of those
Patients requiring baseline
discharged on O2 20 – 28%
O2 were excluded.
were admitted.
Patients admitted after
15%
home O2 for adverse 0
on O2 room air admitted
outcomes. discharged
77. Discharged on Supplemental Oxygen From an
Emergency Department in Patients With Bronchiolitis
Halstead, Pediatrics 2012;129;e605
% patients
60 –
Retrospective chartan
Home O2 is review
of 4194 patients with
effective way to
57%
bronchiolitis between 2005
anddecrease hospital
40 –
2009.
admissions in a
select group
Patients requiring baseline
20 – 28%
O2 were excluded.with
of patients
bronchiolitis.
Patients admitted after
15%
home O2 for adverse 0
on O2 room air admitted
outcomes. discharged
78. Pulmonary surfactant in respiratory syncytial virus
bronchiolitis: The role in pathogenesis and clinical
implications. Barreira Pediatr Pulmonol 2011;46:415
Besides the well-known importance of pulmonary surfactant in
maintenance of pulmonary homeostasis and lung mechanics, the
surfactant proteins SP-A and SP-D are essential components of
the pulmonary innate immune system.
Deficiencies of such proteins, which develop in severe RSV
bronchiolitis, may be related to impairment in viral clearance,
and exacerbated inflammatory response.
79. Pulmonary surfactant in respiratory syncytial virus
bronchiolitis: The role in pathogenesis and clinical
implications. Barreira Pediatr Pulmonol 2011;46:415
The immune response to RSV infection includes the components
of innate and acquired immunity. Innate immune response
represents the first line of defense against pathogens, and plays
three important functions:
a) detection of pathogens and expression of biological factors
for their eradication,
b) signaling and attraction of immune cells to the site of
infection,
c) trigger of the adaptive immune response. In RSV infection,
innate immune system constitutes the main defense
mechanism against the disease.
Krishnan Viral Immunol 2004; 17: 220
80. Pulmonary surfactant in respiratory syncytial virus
bronchiolitis: The role in pathogenesis and clinical
implications. Barreira Pediatr Pulmonol 2011;46:415
•Pulmonary surfactant proteins SP-A and SP-D represent the first
mean of interaction between the virus and the innate pulmonary
defense.
•Following the disruption of the immune barrier represented by the
lung surfactant proteins, interaction of RSV with the respiratory
tract cells—in particular the epithelial and dendritic cells—triggers
the pulmonary inflammatory response.
•After binding to epithelial cells, RSV is recognized by Toll Like
Receptors (TLR) 3 and 4. The linkage between TLR and RSV through
F glycoprotein induces NFκ-β factor activation, and the subsequent
transcription of genes related to antiviral response.
•Such process induces the release of cytokines and chemokines, and
the recruitment of eosinophils, natural killer, and CD4 lymphocytes
into the airways.
82. An objective study of acid reflux and cough in
children using an ambulatory pHmetry–cough logger
A B Chang Arch Dis Child 2011;96:468
pHmetry-cough logger with
attachments
Children (aged <14 yrs) with
chronic cough.
pHmetry using a specifically
built ambulatory
pHmetry–cough logger
that enabled the simultaneous
ambulatory recording of cough
and pH with a fast (10 Hz)
capture rate.
Coughs within (before & after)
10, 30, 60 and 120s of a reflux
episode (pH<4 for >0.5 s).
83. An objective study of acid reflux and cough in
children using an ambulatory pHmetry–cough logger
A B Chang Arch Dis Child 2011;96:468
Cough preceding a pH drop followed by
another cough
Children (aged <14 yrs) with
chronic cough.
pHmetry using a specifically
built ambulatory
pHmetry–cough logger
that enabled the simultaneous
ambulatory recording of cough
and pH with a fast (10 Hz)
capture rate.
Coughs within (before & after)
10, 30, 60 and 120s of a reflux
episode (pH<4 for >0.5 s).
84. An objective study of acid reflux and cough in
children using an ambulatory pHmetry–cough logger
A B Chang Arch Dis Child 2011;96:468
Cough preceding a pH drop followed by
another cough
Recording from the
Children (aged <14 yrs) with
pHmetry–cough logger
chronic cough.
pHmetry using astudy,
used in this specifically
built ambulatory
which has a capture
pHmetry–cough logger
rate of 10 Hz
that enabled the simultaneous
(40 times the usual
ambulatory recording of cough
commerciallyfast (10 Hz)
and pH with a available
systems,
capture rate.
which has a capture
Coughs within (before & after)
10, 30, 60 and 120s of a reflux
rate of 0.25 Hz).
episode (pH<4 for >0.5 s).
85. An objective study of acid reflux and cough in
children using an ambulatory pHmetry–cough logger
A B Chang Arch Dis Child 2011;96:468
Children (aged <14 yrs) with There were:
chronic cough. • 5628 coughs in 20
pHmetry using a specifically children.
built ambulatory
pHmetry–cough logger • Most coughs (83.9%)
that enabled the simultaneous were independent of a
ambulatory recording of cough reflux event.
and pH with a fast (10 Hz)
capture rate. • The temporal
Coughs within (before & after) relationship between
10, 30, 60 and 120s of a reflux acid reflux and cough
episode (pH<4 for >0.5 s). is unlikely causal.
86. An objective study of acid reflux and cough in
children using an ambulatory pHmetry–cough logger
A B Chang Arch Dis Child 2011;96:468
Children (aged <14 yrs) with There were:
Effect of
chronic cough. • 5628 coughs in 20
pHmetry using a specifically
anti-reflux
built ambulatory
children.
• Most coughs (83.9%)
therapy theloggerto
pHmetry–cough
that enabled
has
simultaneous were independent of a
be strictly
ambulatory recording of cough reflux event.
and pH with a fast (10 Hz)
evaluted in
capture rate. • The temporal
relationship between
individual 120s of a reflux
10, 30, 60 and patient
Coughs within (before & after)
acid reflux and cough
episode (pH<4 for >0.5 s). is unlikely causal.
88. Community-acquired pneumonia in children:
what‟s new? Thomson Thorax 2011;66:927
1) The guideline confirms that no diagnostic tests are necessary in the community
but emphasises the importance of providing families with information,
including advice on management, identifying any deterioration and the
importance of reassessment.
2) Infant vaccination with PCV 7 (seven-valent pneumococcal conjugate
vaccination) started in the UK in 2007 has shown a 19% decrease in admission
rates between 2006 and 2008. In countries such as the USA where PCV 7 has
been available for longer, a decrease in hospital admissions of≈30% is reported.
3) Streptococcus pneumoniae remains by far the most common bacterial cause and
is found in 30-40% of cases as a single or co-pathogen. Group A Streptococcus
contributes 1-7% of cases. Mycoplasma and Chlamydia pneumoniae are found
with variable frequency and are not uncommon in the preschool child.
Harris M, Clark J, Coote N, et al. BTS guidelines for the management of community
acquired pneumonia in children: update 2011. Thorax 2011. doi:10.1136/thoraxjnl-2011-200598
89. Community-acquired pneumonia in children:
what‟s new? Thomson Thorax 2011;66:927
4) Overall viruses account for 30-67% of cases and are most frequent in children
<1 year of age.
5) In the 2002 guidance, clinicians were encouraged to search for a pathogen in
all cases, but this has been revised to more practical guidance that aetiological
investigation be restricted to those with either severe or complicated
disease.
6) The WHO produced a method for standardising the interpretation of chest
radiographs in children, but, even using this, the concordance rate between
trained reviewers was only 48%.
7) Investigation of the use of acute phase reactants as a means of
differentiating aetiology and/or severity of CAP are not of clinical utility
in distinguishing viral from bacterial infections and should not be a routine test.
Harris M, Clark J, Coote N, et al. BTS guidelines for the management of community
acquired pneumonia in children: update 2011. Thorax 2011. doi:10.1136/thoraxjnl-2011-200598
90. Community-acquired pneumonia in children:
what‟s new? Thomson Thorax 2011;66:927
8) Oxygen saturation <92% is an indicator of severity and the need for oxygen
therapy.
9) With the introduction of PCV 13 the likelihood of bacterial pneumonia in a fully
vaccinated child will fall further. Fully vaccinated children <2 years old
presenting with mild symptoms of LRTI need not be treated with antibiotics,
but should be reviewed if symptoms persist.
10)The evidence is that bacterial and viral pneumonia cannot reliably be
distinguished and therefore all other children with a clear clinical diagnosis
of pneumonia should receive antibiotics.
Harris M, Clark J, Coote N, et al. BTS guidelines for the management of community
acquired pneumonia in children: update 2011. Thorax 2011. doi:10.1136/thoraxjnl-2011-200598
91. Community-acquired pneumonia in children:
what‟s new? Thomson Thorax 2011;66:927
11) Amoxicillin is effective, well tolerated and cheap. Macrolide antibiotics
should not be first line but can be added at any age if there is no response
to first-line empirical therapy.
12) Over the age of 6 months to either oral amoxicillin or intravenous penicillin,
and the outcomes were equivalent (with a shorter duration of hospital stay
in the oral group). Oral amoxicillin is therefore the antibiotic of choice
both in the community and in hospital. Intravenous antibiotics should be
reserved for children unable to absorb oral drugs or those presenting with
septicaemia or complicated pneumonia.
13) Now: no intravenous line, no tests, no physiotherapy. Simple oral
antibiotics and supportive care will be effective for the majority of
children with CAP, who will also escape from hospital faster.
Harris M, Clark J, Coote N, et al. BTS guidelines for the management of community
acquired pneumonia in children: update 2011. Thorax 2011. doi:10.1136/thoraxjnl-2011-200598
92. Prediction of Pneumonia in a Pediatric Emergency
Department. Mark, Pediatrics 2011;128:246
A prospective cohort % PATIENTS WITH
study in an urban pediatric RADIOGRAPHIC PNEUMONIAE
emergency department 20 –
of patients who had a
chest radiograph
performed for suspicion 16%
of pneumonia (n=2574).
10 –
Radiologist interpretation
equivocal cases
of pneumonia
and definite pneumonia.
0
93. Prediction of Pneumonia in a Pediatric Emergency
Department. Mark, Pediatrics 2011;128:246
A prospective cohort % PATIENTS WITH
study in an urban pediatric RADIOGRAPHIC PNEUMONIAE
emergencyof chest pain, 20 –
History department
of patients who had a
focal rales,
chest radiographfever,
duration of
performed for suspicion
and oximetry levels
16%
of pneumonia (n=2574).
at triage 10 –
were significant
Radiologist interpretation
predictors
equivocal pneumonia.
of cases
of pneumonia
and definite pneumonia.
0
94. Prediction of Pneumonia in a Pediatric Emergency
Department. Mark, Pediatrics 2011;128:246
A prospective cohort OR FOR PNEUMONIAE
study in an urban pediatric
4 –
emergency department
of patients who had a
chest radiograph 3 – 3.6
performed for suspicion
of pneumonia (n=2574). 2 –
Radiologist interpretation 1 –
equivocal cases
of pneumonia
and definite pneumonia. 00
OXIGEN SATURATION ≤92%
95. Prediction of Pneumonia in a Pediatric Emergency
Department. Mark, Pediatrics 2011;128:246
A prospective cohort
Among subjects with OR FOR PNEUMONIAE
study inSaO >92%,
an urban pediatric
2 4 –
emergency department
no history of fever,
of patients who had a
no focal decreased
chest breath sounds,
radiograph 3 – 3.6
performed focal rales,
and no for suspicion
of pneumonia (n=2574). 2 –
the rate of
radiographic pneumonia
Radiologist interpretation
was 7.6% 1 –
equivocal cases
of pneumoniaand
and definite pneumonia
definite pneumonia. 00
OXIGEN SATURATION ≤92%
was 2.9%
96. Role of Procalcitonin in Managing Adult Patients
With Respiratory Tract Infections
Schuetz P, Chest 2012;141:1055
A growing body of evidence supports the use of procalcitonin (PCT) to
differentiate bacterial from viral respiratory diagnoses, to help
risk stratify patients, and to guide antibiotic therapy decisions about
initial need for, and optimal duration of, therapy.
A series of randomized controlled trials have evaluated PCT protocols
for antibiotic-related decision making and have included patients from
different clinical settings and with different severities of respiratory
infection.
In these trials, initial PCT levels were effective in guiding decisions
about the initiation of antibiotic therapy in lower-acuity patients, and
subsequent measurements were effective for guiding duration of
therapy in higher-acuity patients, without apparent harmful effects.
97. Role of Procalcitonin in Managing Adult Patients
With Respiratory Tract Infections
Schuetz P, Chest 2012;141:1055
A growing body of evidence supports the use of procalcitonin (PCT) to
differentiate bacterial from viral respiratory diagnoses, to help
risk stratify with any other laboratory test, PCT about
As patients, and to guide antibiotic therapy decisions
initial should not optimal durationa stand-alone basis.
need for, and be used on of, therapy.
Rather, it must be integrated into clinical
A series of randomized controlled trials have evaluated PCT protocols
protocols, together with clinical,
for antibiotic-related decision making and have included patients from
different clinical settings and with different severities of respiratory
microbiologic data and with results from
infection.
clinical risk scores.
In these trials, initial PCT levels were effective in guiding decisions
about the initiation of antibiotic therapy in lower-acuity patients, and
subsequent measurements were effective for guiding duration of
therapy in higher-acuity patients, without apparent harmful effects.
98. Role of Procalcitonin in Managing Adult Patients
With Respiratory Tract Infections
Schuetz P, Chest 2012;141:1055
Use of PCT
99. Role of Procalcitonin in Managing Adult Patients
With Respiratory Tract Infections
Schuetz P, Chest 2012;141:1055
Use of PCT
100. Role of Procalcitonin in Managing Adult Patients
With Respiratory Tract Infections
Schuetz P, Chest 2012;141:1055
Use of PCT
The evidence suggests that using PCT
for patients with respiratory infections
can lead to more parsimonious antibiotic use
and de-escalation, without safety concerns
101. Procalcitonin and C-reactive protein in hospitalized adult
patients with community-acquired pneumonia or
exacerbation of asthma or COPD
Bafadhel CHEST 2011;139:1410
62 patients with
pneumonia, 96 with
asthma and 161 with
COPD were studied
Serum procalcitonin
(PCT) and C-reactive
protein (CRP) were
assayed in these
patients
102. Procalcitonin and C-reactive protein in hospitalized adult
patients with community-acquired pneumonia or
exacerbation of asthma or COPD
Bafadhel CHEST 2011;139:1410
62 patients with
pneumonia, 96 with
asthma and 161 with
COPD were studied
Serum procalcitonin
(PCT) and C-reactive
protein (CRP) were
assayed in these
patients
103. Procalcitonin and C-reactive protein in hospitalized adult
patients with community-acquired pneumonia or
exacerbation of asthma or COPD
Bafadhel CHEST 2011;139:1410
Patients with pneumonia
had increased PCT and
CRP levels compared
with those with asthma
and COPD
104. Procalcitonin and C-reactive protein in hospitalized adult
patients with community-acquired pneumonia or
exacerbation of asthma or COPD
Bafadhel CHEST 2011;139:1410
62 patients with
A CRP value >48
pneumonia, 96 with
mg/L had a
asthma and 161
sensitivity of
with COPD were
91% and
studied
specificity of
Serum procalcitonin
93% for
(PCT) and C-reactive
identifying
protein (CRP) were
patients with
assayed in these
pneumonia
105. Procalcitonin and C-reactive protein in hospitalized adult
patients with community-acquired pneumonia or
exacerbation of asthma or COPD
Bafadhel CHEST 2011;139:1410
62 patients with
CRP levels could
pneumonia, 96 with
be used to guide
asthma and 161
antibiotic therapy
with COPD were
and reduce
studied
antibiotic overuse
Serum procalcitonin
in hospitalized
(PCT) and C-reactive
patients with
protein respiratory
acute (CRP) were
assayed in these
illness
106. Procalcitonin and C-reactive protein in hospitalized adult
patients with community-acquired pneumonia or
exacerbation of asthma or COPD
Bafadhel CHEST 2011;139:1410
Serum Pct and CRP
concentrations were
strongly correlated
p<0.001 r=0.56
108. Alcohol drinking and risk of subsequent hospitalisation
with pneumonia. Kornum J.B, Eur Respir J 2012;39:149
1) Alcohol abuse has been associated with a
2-to 9-fold higher risk of pneumonia.
2) Abuse of alcohol may increase susceptibility
to pneumonia for several reasons:
alcohol intake may cause alterations in
neutrophil and macrophage function and
abnormalities in ciliary and surfactant functioning in the lung .
Alcohol overuse also can increase the risk of aspiration and
suppress the normal cough reflex .
3) Finally, chronic alcohol intake is closely associated with
malnutrition and other chronic diseases that may affect
pneumonia risk.
109. Alcohol drinking and risk of subsequent hospitalisation
with pneumonia. Kornum J.B, Eur Respir J 2012;39:149
HR for pneumonia
2 –
* 1.81
22,485 males and
* 1.49
24,682 females from
Denmark * 1.15
(aged 50–64 yrs). 1 – * 1.0
* 0.88
* 0.87
follow-up of 12 yrs.
1,091 (males) and
944 (females) had 0
pneumonia-related 0 1-6 7-20 21-34 34-50 > 50
hospitalisation.
drinks for week
110. Alcohol drinking and risk of subsequent hospitalisation
with pneumonia. Kornum J.B, Eur Respir J 2012;39:149
HR for pneumonia
Regular moderate 2 –
alcohol intake is
* 1.81
not associated
22,485increased risk
with males and * 1.49
24,682 females from
of hospitalisation
Denmark * 1.15
for pneumonia. 1 –
(aged High weekly
50–64 yrs). * 1.0
* 0.88
alcohol consumption * 0.87
follow-up of 12 yrs.
and infrequent
heavy drinking may
1,091 (males) and
increase pneumonia
944 (females) had
risk 0
pneumonia-related 0 1-6 7-20 21-34 34-50 > 50
hospitalisation.
drinks for week
111. Adhesion of Streptococcus pneumoniae to human airway
epithelial cells exposed to urban particulate matter
Mushtaq JACI 2011;127:1236
Background
Epidemiologic studies report an association between pneumonia
and urban particulate matter (PM) less than 10 microns (μm) in
aerodynamic diameter (PM10).
Streptococcus pneumoniae is a common cause of bacterial
pneumonia worldwide. To date, the mechanism whereby urban
PM enhances vulnerability to S pneumoniae infection is unclear.
Adhesion of S pneumoniae to host cells is a prerequisite for
infection. Host-expressed proteins, including the receptor for
platelet-activating factor (PAFR), are co-opted by S pneumoniae
to adhere to lower airway epithelial cells.
112. Adhesion of Streptococcus pneumoniae to human airway
epithelial cells exposed to urban particulate matter
Mushtaq JACI 2011;127:1236
1) Cultured with PM10 and PM2.5
2) Then infected with S pneumoniae
Airway epithelial cells A 549
PM10 and PM2.5 increased
S pneumoniae adhesion
113. Adhesion of Streptococcus pneumoniae to human airway
epithelial cells exposed to urban particulate matter
Mushtaq JACI 2011;127:1236
1) Cultured with PM10 and PM2.5
2) Then infected with S pneumoniae
Airway epithelial cells A 549
PM10 and PM2.5 increased
S pneumoniae adhesion
Adhesion was attenuated
by N-acetyl cysteine
antioxidant
114. Adhesion of Streptococcus pneumoniae to human airway
epithelial cells exposed to urban particulate matter
Mushtaq JACI 2011;127:1236
1) Cultured with PM10 and PM2.5
2) Then infected with S pneumoniae
Airway epithelial cells A 549
PM10 and PM2.5 increased PM
The ability of combustion
to induce oxidative stress in
S pneumoniae adhesion
airway cells is considered to
be an important factor in the
initiation of adverse health
Adhesion was attenuated effects.
by N-acetyl cysteine
antioxidant
115. Influenza Coinfection and Outcomes in Children
With Complicated Pneumonia. Williams APAM 2011;165:506
A bacterial pathogen was identified
in 1201 cases (35.5%).
The most commonly identified
3382 children bacteria were
discharged from
Staphylococcus aureus
hospitals with
in children with
complicated
influenza coinfection
pneumonia (22.9% of cases)
requiring a and
pleural drainage. Streptococcus pneumoniae
in children without coinfection
(20.0% of cases).
116. Influenza Coinfection and Outcomes in Children
With Complicated Pneumonia. Williams APAM 2011;165:506
Multivariable analysis comparing outcomes
between patients with complicated pneumonia
with and without influenza
117. Influenza Coinfection and Outcomes in Children
With Complicated Pneumonia. Williams APAM 2011;165:506
Multivariable analysis comparing outcomes
between patients with complicated pneumonia
with and without influenza
Influenza coinfection
was associated with
higher odds of
intensive care unit
admission,
mechanical ventilation,
vasoactive infusions,
blood product
transfusions,
higher costs
and a
longer hospital stay.
118. Influenza vaccination is associated with reduced severity
of community-acquired pneumonia Tessmer ERJ 2011;38:147
Pneumonia is an important cause of influenza-associated
morbidity and mortality.
Influenza vaccination has been shown to reduce morbidity and
mortality during influenza seasons.
Protection from severe pneumonia may contribute to the
beneficial effect of influenza vaccination.
Therefore, we investigated the impact of prior influenza
vaccination on disease severity and mortality in patients
with community-acquired pneumonia (CAP).
119. Influenza vaccination is associated with reduced severity
of community-acquired pneumonia Tessmer ERJ 2011;38:147
During the influenza
season in vaccinated
subjects OR
1.0 –
Patients were
analysed separately
as an influenza
0.76
0.53
season (2.368 0.5 –
patients) and
off-season cohort.
Vaccination status.
0
Severe Procalcitonin
pneumonia ≥2.0 ng/ml
120. Influenza vaccination is associated with reduced severity
of community-acquired pneumonia Tessmer ERJ 2011;38:147
During the influenza
season in vaccinated
subjects OR
These patients 1.0 –
Patients were a
showed
analysed separately
significantly
as an influenza
0.76
better overall
0.53
season and 2.368 0.5 –
survival within the
off-season cohort.
6-month
Vaccination status.
follow-up period. 0
Severe Procalcitonin
pneumonia ≥2.0 ng/ml
121. Influenza vaccination is associated with reduced severity
of community-acquired pneumonia Tessmer ERJ 2011;38:147
During the influenza
season in vaccinated
subjects OR
1.0 –
Within the
Patients were cohort
off-season
analysed separately
(2,632 patients)
as an influenza
0.76
there was no
0.53
season (2.368 0.5 –
patients) and influence
significant
of vaccination
off-season cohort.
status on CAP
Vaccination status.
severity 0
Severe Procalcitonin
pneumonia ≥2.0 ng/ml
122. Microbial evaluation of proton-pump inhibitors
and the risk of pneumonia Meijvis ERJ 2011;38:1165
Recent initiation of proton-pump inhibitor (PPI) treatment may
increase the risk of community-acquired pneumonia (CAP),
hypothetically by allowing colonisation of the oropharynx
by gastrointestinal bacteria.
123. Microbial evaluation of proton-pump inhibitors
and the risk of pneumonia Meijvis ERJ 2011;38:1165
OR for community
acquired pneumonia.
3.1
3 –
430 cases with 2 –
pneumonia.
1720 controls.
1 –
0
Recent initiation of PPI
treatment (<30 days).
124. Microbial evaluation of proton-pump inhibitors
and the risk of pneumonia Meijvis ERJ 2011;38:1165
OR for community
acquired pneumonia.
Gastrointestinal
3.1
3 –
bacteria were
identified in only 5
430 cases with
(1.2%) patients with
pneumonia.
2 –
pneumonia
1720 controls.
(2 current users and
1 –
3 nonusers).
0
Recent initiation of PPI
treatment (<30 days).
125. Microbial evaluation of proton-pump inhibitors
and the risk of pneumonia Meijvis ERJ 2011;38:1165
OR for community
acquired pneumonia.
PPIs is associated with
3.1
an increased risk of 3 –
CAP, especially when
430 cases with recently2 –
treatment has
pneumonia. started
been
1720 controls. in microbial
but no shifts
aetiology seem 1 –
to explain
the associations.
0
Recent initiation of PPI
treatment (<30 days).
126. Increased incidence of bronchopulmonary
fistulas complicating pediatric pneumonia
McKee Pediatr Pulmonol 2011;46:717
Background
The frequency of complicated
pneumococcal disease, including necrotizing
pneumonia, has increased over the last
decade.
During 2008–2009, we noted an increase in
the number of children whose empyema
was complicated by the development of a
bronchopleural fistula and air leak.
We studied these children to see if there
was an associated cause.
127. Increased incidence of bronchopulmonary
fistulas complicating pediatric pneumonia
McKee Pediatr Pulmonol 2011;46:717
% children with fistula
35 – 33%
Retrospective review of
30 –
children admitted with a
parapneumonic effusion 25 –
or empyema from 20 –
p<0.0001
2002 to 2007, compared 15 –
with 2008 to 2009.
10 –
310 children. 05 –
00
1%
2002-2007 2008-2009
128. Increased incidence of bronchopulmonary
fistulas complicating pediatric pneumonia
McKee Pediatr Pulmonol 2011;46:717
% children with fistula
35 – 33%
Retrospective review of
Pneumococcal serotype 30 –
children admitted with a
3 was identified in
parapneumonic effusion
10/16 (63%) children
25 –
orwith a bronchopleural
empyema from 20 –
p<0.0001
2002 to 2007, compared
fistula and 1/33 (3%) 15 –
withwithout (<0.0001).
2008 to 2009.
10 –
310 children. 05 –
00
1%
2002-2007 2008-2009
129. Increased incidence of bronchopulmonary
fistulas complicating pediatric pneumonia
McKee Pediatr Pulmonol 2011;46:717
% children with fistula
35 – 33%
Retrospective review of
Pneumococcal serotype 30 –
children admitted with a
3 infection, was not
parapneumonic effusion
covered by the
25 –
or empyema from 20 –
p<0.0001
heptavalent
2002 to 2007, compared
pneumococcal 15 –
with 2008 to 2009.
vaccine Prevenar. 10 –
310 children. 05 –
00
1%
2002-2007 2008-2009
130. Combined treatment for child refractory
Mycoplasma pneumoniae pneumonia with ciprofloxacin
and glucocorticoid. Lu Pediatr Pulmonol 2011;46:1093
Mycoplasma pneumoniae (M. pneumoniae) is one of the major
pathogens causing community-acquired respiratory tract
infections in children.
Although M. pneumoniae pneumonia (MP) is usually a benign
self-limited disease, it may develop into a severe life-threatening
pneumonia in rare cases.
These cases are defined as refractory MP showing clinical and
radiological deterioration after macrolide antibiotic therapy
for 7 days or more.
131. Combined treatment for child refractory
Mycoplasma pneumoniae pneumonia with ciprofloxacin
and glucocorticoid. Lu Pediatr Pulmonol 2011;46:1093
Mycoplasma pneumoniae (M. pneumoniae) is one of the major
pathogens causing community-acquired respiratory tract
infections in children.
Refractory MP may be related to emergency
Although M. pneumoniae pneumonia (MP) pneumoniae benign
of macrolide (ML) resistant M.
is usually a
self-limited disease, it may develop into a severe life-threatening
pneumonia in rare cases.
These cases are defined as refractory MP showing clinical and
radiological deterioration after macrolide antibiotic therapy
for 7 days or more.
132. Combined treatment for child refractory
Mycoplasma pneumoniae pneumonia with ciprofloxacin
and glucocorticoid. Lu Pediatr Pulmonol 2011;46:1093
In children, macrolide antibiotics are the first-choice agents
for M. pneumoniae infections, and these antibiotics have been
thought to have excellent effectiveness against M. pneumoniae
for many years.
However, in recent years, many isolates of M. pneumoniae
from clinical samples showed resistance to macrolides.
Mutations in domain V of 23S rRNA of M. pneumoniae are
proved as main mechanism of resistance.
133. Combined treatment for child refractory
Mycoplasma pneumoniae pneumonia with ciprofloxacin
and glucocorticoid. Lu Pediatr Pulmonol 2011;46:1093
In children, macrolide antibiotics are the first-choice agents
for M. pneumoniae infections, and these antibiotics have been
thought to have excellent effectiveness against M. pneumoniae
Fluoroquinolones have a broad spectrum of
for many years.
activity against Gram-positive, Gram-negative,
and other organisms such as Mycoplasma
However, in recent years, many isolates of M. pneumoniae
and Chlamydia.
from clinical samples showed resistance to macrolides.
Mutations in domain V of 23S rRNA of M. pneumoniae are
proved as main mechanism of resistance.
134. Combined treatment for child refractory
Mycoplasma pneumoniae pneumonia with ciprofloxacin
and glucocorticoid. Lu Pediatr Pulmonol 2011;46:1093
In children, macrolide antibiotics are the first-choice agents
for M. pneumoniae infections, and these antibiotics have been
thought to have excellent effectiveness against M. pneumoniae
Many clinical studies show that corticosteroids
for many years.
dramatically benefit patients with severe MP,
However, in recent years, many isolates of immunity in
which is related to cell-mediated M. pneumoniae
from clinical samplespneumoniae infections.
M. showed resistance to macrolides.
Mutations in domain V of 23S rRNA of M. pneumoniae are
proved as main mechanism of resistance.
136. Lactate as a predictor of mortality in Malawian children
with WHO-defined pneumonia.
Ramakrishna, Arch Dis Child 2012;97:336
• Currently the best predictor of pneumonia mortality risk
is arterial oxygen saturation, measured by pulse oximetry
(saturation of peripheral oxygen, SpO2).
• Lactate is a product of anaerobic cellular metabolism.
It is used as a marker of poor tissue oxygen delivery,
and cell hypoxia in high-income settings to monitor critically ill
children, including those with severe infections, low cardiac output
and acute respiratory distress syndrome.
• Elevated blood lactate may occur as an end result of:
- hypoxaemic respiratory failure
- cardiovascular or cellular failure from associated sepsis.
137. Lactate as a predictor of mortality in Malawian children
with WHO-defined pneumonia.
Ramakrishna, Arch Dis Child 2012;97:336
% deaths
20 –
233 children 18%
15 –
with pneumonia.
Serum lactate
13%
10 –
concentration.
05 –
00
2.1 – 4.0 > 4.0
Lactate concentration (mmol/l)
138. Lactate as a predictor of mortality in Malawian children
with WHO-defined pneumonia.
Ramakrishna, Arch Dis Child 2012;97:336
RR of death
8 –
233 children
7 –
6 –
7.48
with pneumonia.
5 –
Serum lactate 4 –
concentration.
3 –
2 –
1 –
0
Lactate level >2 mmol/l
139. Lactate as a predictor of mortality in Malawian children
with WHO-defined pneumonia.
Ramakrishna, Arch Dis Child 2012;97:336
Log-likelihood model of saturation
of peripheral oxygen (SpO2) according to
normal and elevated lactate concentrations.
233 children
with pneumonia.
Serum lactate
concentration.
140. Lactate as a predictor of mortality in Malawian children
with WHO-defined pneumonia.
Ramakrishna, Arch Dis Child 2012;97:336
Log-likelihood model of saturation
of peripheral oxygen (SpO2) according to
Used in conjunction normal and elevated lactate concentrations.
with clinical
risk factors
233 children and
pulse oximetry
with pneumonia. ,
lactate could play
Serum lactate role
an important
concentration. the
in identifying
sickest patients
with pneumonia in
developing countries.
141. Lactate as a predictor of mortality in Malawian children
with WHO-defined pneumonia.
Ramakrishna, Arch Dis Child 2012;97:336
• Hypoxaemia occurs in pneumonia because of ventilation–perfusion
mismatching in the lungs, right to left intrapulmonary shunts, and
in very severe and late stages due to inadequate minute volume.
• Tissue hypoxaemia and high blood lactate can occur because
of low partial pressure of arterial oxygen, or impaired perfusion,
impaired oxygen delivery or impaired oxygen extraction
from a septic state that exists in some children with bacteraemia.
• Hypoxaemia may lead to increased serum lactate, though the
hypoxemic threshold for hyperlactataemia will differ between
individuals.
65 out of 87 children with hypoxaemia by definition (SpO2 <90%)
had normal lactate concentrations.
142. Lactate as a predictor of mortality in Malawian children
with WHO-defined pneumonia.
Ramakrishna, Arch Dis Child 2012;97:336
• Children with radiographic consolidation or effusion
had lower risk of mortality when compared to children
with evidence of interstitial infiltrate and hyperinflation.
• Radiographic findings of interstitial infiltrate,
peribronchial thickening, small areas of atelectasis
and hyperinflation are features of Pneumocystis jirovecii
pneumonia, as well as being consistent with viral pneumonia.