What 2012 pulmonology

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What 2012 pulmonology

  1. 1. WHAT YOU SHOULD HAVE READ BUT….2012  pulmonologyAttilio BonerUniversity ofVerona, Italy
  2. 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. 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. 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. 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. 6. Lung function prior to viral lower respiratory tract infections in prematurely born infants Drysdale Thorax 2011;66:468ObjectivePrematurely born infants who develop respiratory syncytial virus(RSV) lower respiratory tract infections (LRTIs) have lungfunction abnormalities at follow-up.The aim of this study was to determine whether prematurely borninfants who developed symptomatic RSV, or other viral LRTI(s),had poorer premorbid lung function than infants who did notdevelop LRTIs during the RSV season. ?
  7. 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. 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. 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. 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. 11. Viral-mediated Inhibition of Antioxidant Enzymes Contributes to the Pathogenesis of Severe RespiratorySyncytial Virus Bronchiolitis Hosakote AJRCCM 2012;183:1550RationaleRespiratory syncytial virus (RSV) is a major cause of lower respiratorytract infections in children, for which no specific treatment or vaccineis currently available.We have previously shown that RSV induces reactive oxygen species incultured cells and oxidative injury in the lungs of experimentallyinfected mice. The mechanism(s) of RSV-induced oxidative stress invivo is not known.ObjectivesTo measure changes of lung antioxidant enzymes expression/activityand activation of NF-E2-related factor 2 (Nrf2), a transcription factorthat regulates detoxifying and antioxidant enzyme gene expression, inmice and in infants with naturally acquired RSV infection.
  12. 12. Viral-mediated Inhibition of Antioxidant Enzymes Contributes to the Pathogenesis of Severe RespiratorySyncytial 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. 13. Viral-mediated Inhibition of Antioxidant Enzymes Contributes to the Pathogenesis of Severe RespiratorySyncytial 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. 14. Viral-mediated Inhibition of Antioxidant Enzymes Contributes to the Pathogenesis of Severe RespiratorySyncytial 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. 15. Viral-mediated Inhibition of Antioxidant Enzymes Contributes to the Pathogenesis of Severe RespiratorySyncytial 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. 16. Viral-mediated Inhibition of Antioxidant Enzymes Contributes to the Pathogenesis of Severe RespiratorySyncytial Virus Bronchiolitis Hosakote AJRCCM 2012;183:1550 Antioxidant enzymes are reduced in bronchoalveolar lavage (BAL) of respiratory syncytial virus (RSV)-infected mice.
  17. 17. Viral-mediated Inhibition of Antioxidant Enzymes Contributes to the Pathogenesis of Severe RespiratorySyncytial 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. 18. Viral-mediated Inhibition of Antioxidant Enzymes Contributes to the Pathogenesis of Severe RespiratorySyncytial Virus Bronchiolitis Hosakote AJRCCM 2012;183:1550Superoxide 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. 19. Viral-mediated Inhibition of Antioxidant Enzymes Contributes to the Pathogenesis of Severe RespiratorySyncytial 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. 20. Viral-mediated Inhibition of Antioxidant Enzymes Contributes to the Pathogenesis of Severe RespiratorySyncytial 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. 21. Viral-mediated Inhibition of Antioxidant Enzymes Contributes to the Pathogenesis of Severe RespiratorySyncytial 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. 22. Viral-mediated Inhibition of Antioxidant Enzymes Contributes to the Pathogenesis of Severe RespiratorySyncytial Virus Bronchiolitis Hosakote AJRCCM 2012;183:1550Antioxidant enzyme expression in nasopharyngeal secretions (NPS) of infants with naturally acquired respiratory syncytial virus (RSV) infections.
  23. 23. Viral-mediated Inhibition of Antioxidant Enzymes Contributes to the Pathogenesis of Severe RespiratorySyncytial Virus Bronchiolitis Hosakote AJRCCM 2012;183:1550Antioxidant 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. 24. Viral-mediated Inhibition of Antioxidant Enzymes Contributes to the Pathogenesis of Severe RespiratorySyncytial Virus Bronchiolitis Hosakote AJRCCM 2012;183:1550ConclusionRSV infection induces a significant decrease in the expression ofmost antioxidant enzyme involved in maintaining cellularoxidant–antioxidant balance in mice and children.The exception is SOD 2, for which levels are reduced in the BALof infected mice but not in epithelial cell proteins of the conductiveairways or in nasopharyngeal secretions of infected children,suggesting that airway epithelial cells may not be the only cellularsource of the lung antioxidant response measured in BAL of mice.Other tissue resident cells, such as alveolar macrophages, whichare early targets of RSV infection, could contribute to theobserved BAL findings.
  25. 25. Rhinovirus-induced bronchiolitis and asthma development Jartti Pediat Allergy Immunol 2011;22:350The association between any sensitization The association between log10 numberand of sensitizations andsole 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 wassole other virus (n = 8), sensitized; not computable),mixed virus (n = 87) and mixed virus, andnon-virus (n = 13) non-virusassociated wheezing in hospitalized children. associated wheezing in hospitalized children.
  26. 26. Rhinovirus-induced bronchiolitis and asthma development Jartti Pediat Allergy Immunol 2011;22:350The association between any sensitization The association between log10 numberand of sensitizations andsole rhinovirus [human rhinovirus (HRV);n= 58], sole HRV,sole respiratory syncytial virus [respiratory sole RSV, Low interferon responses have beensyncytial 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 wassole other virus (n = 8), sensitized; not computable),mixed virus (n = 87) and mixed virus, andnon-virus (n = 13) non-virusassociated wheezing in hospitalized children. associated wheezing in hospitalized children.
  27. 27. Rhinovirus-induced bronchiolitis and asthma development Jartti Pediat Allergy Immunol 2011;22:350The association between any sensitization The association between log10 numberand of sensitizations andsole rhinovirus [human rhinovirus (HRV);n= 58], sole HRV, Although recurrent wheezing is common aftersole 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 ofsole human bocavirus (HBoV; n = 12), persistent wheezing until 6 years of age andsole other virus (n = 8), sensitized; not computable),mixed virus (n = 87) and for childhood asthma. and mixed virus,non-virus (n = 13) non-virusassociated wheezing in hospitalized children. associated wheezing in hospitalized children.
  28. 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. 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. 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. 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. 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. 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. 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. 35. Clinical Impact of RT-PCR for Pediatric Acute Respiratory Infections: A Controlled Clinical Trial Wishaupt Pediatrics 2011;128:e11131. 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. 36. Clinical Impact of RT-PCR for Pediatric Acute Respiratory Infections: A Controlled Clinical Trial Wishaupt Pediatrics 2011;128:e11133. 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. 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. 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. 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 observations32 (≥4h) was 32h.
  40. 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. 41. Observational study of two oxygen saturation targets for discharge in bronchiolitis Cunningham, Arch Dis Child 2012;97:3611. 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. 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. 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. 44. Clinical predictors of admission in infants with acute bronchiolitis Marlais Arch Dis Child 2011;96:648 Bronchiolitis risk of admission score
  45. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 57. Unnecessary Care for Bronchiolitis Decreases With Increasing Inpatient Prevalence of Bronchiolitis Van Cleve Pediatrics 2011;128:e11061. 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. 58. Unnecessary Care for Bronchiolitis Decreases With Increasing Inpatient Prevalence of Bronchiolitis Van Cleve Pediatrics 2011;128:e11063. 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. 59. Unnecessary Care for Bronchiolitis Decreases With Increasing Inpatient Prevalence of Bronchiolitis Van Cleve Pediatrics 2011;128:e11066. Failure to incorporate such information might lead to an inappropriatelylow degree of faith in a clinical diagnosis, which might contribute tooveruse of diagnostic tests and empirical therapeutic measures.7.In this study, we hypothesized that an important determinant of caredelivery to patients with eventual diagnoses of bronchiolitis would be theinpatient bronchiolitis prevalence (IBP) in the hospital in which their care isbeing delivered. A priori, we postulated that an elevated IBP would increasephysician/care team confidence that a patient‘s illness was caused bybronchiolitis and therefore would decrease the likelihood that the patientwould receive care that is generally thought to provide little or no benefitfor bronchiolitis.
  60. 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. 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. 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. 63. Helium-Oxygen Therapy for Infants With Bronchiolitis Kim APAM 2011;165:1115 Lowell Pediatrics 1987;79:939.
  64. 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. 65. Helium-Oxygen Therapy for Infants With Bronchiolitis Kim APAM 2011;165:1115 Mean Respiratory Distress Assessment Instrument (RDAI) scores vs time.
  66. 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. 67. Clinical predictors of nasal continuous positive airway pressure requirement in acute bronchiolitis Evans Pediatr Pulmonol 2012;47:3811) 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. 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. 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 pointchange in the independent variable, i.e., odds ratio for a 1 point change in the unit of measurement forcontinuous variable and odds ratio associated with the presence of a binary variable.
  70. 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. 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. 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. 73. Discharged on Supplemental Oxygen From anEmergency Department in Patients With Bronchiolitis Halstead, Pediatrics 2012;129;e6051) 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. 74. Discharged on Supplemental Oxygen From an Emergency Department in Patients With Bronchiolitis Halstead, Pediatrics 2012;129;e605 The American Academy of Pediatrics1) 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 intensity2) 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. 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. 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. 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. 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. 79. Pulmonary surfactant in respiratory syncytial virus bronchiolitis: The role in pathogenesis and clinical implications. Barreira Pediatr Pulmonol 2011;46:415The immune response to RSV infection includes the componentsof innate and acquired immunity. Innate immune responserepresents the first line of defense against pathogens, and playsthree 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. 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 firstmean of interaction between the virus and the innate pulmonarydefense.•Following the disruption of the immune barrier represented by thelung surfactant proteins, interaction of RSV with the respiratorytract cells—in particular the epithelial and dendritic cells—triggersthe pulmonary inflammatory response.•After binding to epithelial cells, RSV is recognized by Toll LikeReceptors (TLR) 3 and 4. The linkage between TLR and RSV throughF glycoprotein induces NFκ-β factor activation, and the subsequenttranscription of genes related to antiviral response.•Such process induces the release of cytokines and chemokines, andthe recruitment of eosinophils, natural killer, and CD4 lymphocytesinto the airways.
  81. 81. •cough
  82. 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. 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. 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. 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. 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 betweenindividual 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.
  87. 87. Pnumonia
  88. 88. Community-acquired pneumonia in children: what‟s new? Thomson Thorax 2011;66:9271) 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. 89. Community-acquired pneumonia in children: what‟s new? Thomson Thorax 2011;66:9274) 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. 90. Community-acquired pneumonia in children: what‟s new? Thomson Thorax 2011;66:9278) 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. 91. Community-acquired pneumonia in children: what‟s new? Thomson Thorax 2011;66:92711) 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. 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. 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. 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. 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. 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. 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. 98. Role of Procalcitonin in Managing Adult Patients With Respiratory Tract Infections Schuetz P, Chest 2012;141:1055 Use of PCT
  99. 99. Role of Procalcitonin in Managing Adult Patients With Respiratory Tract Infections Schuetz P, Chest 2012;141:1055 Use of PCT
  100. 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. 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. 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. 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. 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. 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. 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
  107. 107. PnumoniaRisk factors
  108. 108. Alcohol drinking and risk of subsequent hospitalisation with pneumonia. Kornum J.B, Eur Respir J 2012;39:1491) 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. 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. 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. 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. 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. 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. 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. 115. Influenza Coinfection and Outcomes in ChildrenWith 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. 116. Influenza Coinfection and Outcomes in ChildrenWith Complicated Pneumonia. Williams APAM 2011;165:506 Multivariable analysis comparing outcomes between patients with complicated pneumonia with and without influenza
  117. 117. Influenza Coinfection and Outcomes in ChildrenWith 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. 118. Influenza vaccination is associated with reduced severityof 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. 119. Influenza vaccination is associated with reduced severityof 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. 120. Influenza vaccination is associated with reduced severityof 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. 121. Influenza vaccination is associated with reduced severityof 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. 122. Microbial evaluation of proton-pump inhibitorsand the risk of pneumonia Meijvis ERJ 2011;38:1165Recent 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. 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. 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. 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. 126. Increased incidence of bronchopulmonary fistulas complicating pediatric pneumonia McKee Pediatr Pulmonol 2011;46:717BackgroundThe frequency of complicatedpneumococcal disease, including necrotizingpneumonia, has increased over the lastdecade.During 2008–2009, we noted an increase inthe number of children whose empyemawas complicated by the development of abronchopleural fistula and air leak.We studied these children to see if therewas an associated cause.
  127. 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. 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. 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. 130. Combined treatment for child refractoryMycoplasma 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. 131. Combined treatment for child refractoryMycoplasma 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. 132. Combined treatment for child refractoryMycoplasma 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. 133. Combined treatment for child refractoryMycoplasma 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. 134. Combined treatment for child refractoryMycoplasma 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.
  135. 135. Pnumoniaassesment
  136. 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. 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. 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. 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.

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