Pulmonology

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Pulmonology

  1. 1. WHAT YOU SHOULD HAVE READ BUT….2010 <ul><li>pulmonology </li></ul>University of Verona, Italy Attilio Boner
  2. 2. Bronchiolitis
  3. 3. Bronchiolitis Risk factors
  4. 4. Influence of Ambient Air Pollutant Sources on Clinical Encounters for Infant Bronchiolitis Karr AJRCCM 2009:180:995 <ul><li>Infants with bronchiolitis (n = 11,675) matched to control subjects. </li></ul>IN INFANTS WHO LIVED WITHIN 50 METERS OF A MAJOR HIGHWAY % Increase in the Risk of Hospitalization for Bronchiolitis 6% 10 – 9 – 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0
  5. 5. Influence of Ambient Air Pollutant Sources on Clinical Encounters for Infant Bronchiolitis Karr AJRCCM 2009:180:995 <ul><li>Infants with bronchiolitis (n = 11,675) matched to control subjects. </li></ul>IN INFANTS WHO LIVED WITHIN 50 METERS OF A MAJOR HIGHWAY % Increase in the Risk of Hospitalization for Bronchiolitis 6% 10 – 9 – 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 Increase in lifetime exposure to NO 2 , NO, SO 2 , CO, was associated with increased risk of bronchiolitis.
  6. 6. Cigarette Smoke Alters Respiratory Syncytial Virus–Induced Apoptosis and Replication Groskreutz Am J Respir Cell Mol Biol 2009;41:189 Exposed to cigarette smoke extract for 2 days Primary airway epithelial cells Followed by 1 day of RSV exposure Less apoptosis when cells were treated with cigarette smoke before viral infection. Viral load was increased.
  7. 7. Cigarette Smoke Alters Respiratory Syncytial Virus–Induced Apoptosis and Replication Groskreutz Am J Respir Cell Mol Biol 2009;41:189 Exposed to cigarette smoke extract for 2 days Primary airway epithelial cells Followed by 1 day of RSV exposure Less apoptosis when cells were treated with cigarette smoke before viral infection. Viral load was increased. Cigarette smoke causes necrosis rather than apoptosis in viral infection, resulting in increased inflammation and enhanced viral replication.
  8. 8. Cytokine responses in cord blood predict the severity of later respiratory syncytial virus infection Juntti JACI 2009;124:52 Background: It has been claimed that an early respiratory syncytial virus (RSV) infection can induce asthma and recurrent wheezing. Objective: We addressed the question of whether infants contracting an early RSV infection differ from healthy children in their cytokine production at birth.
  9. 9. Cytokine responses in cord blood predict the severity of later respiratory syncytial virus infection Juntti JACI 2009;124:52 <ul><li>cord blood samples from 1084 newborns (birth cohort) </li></ul><ul><li>47 of these newborns with RSV infection before 6 months of age. </li></ul><ul><li>had higher LPS-stimulated combined IL-6 and IL-8 responses than the infants treated as outpatients ( P = .005). </li></ul><ul><li>showed lower IL-1β, IL-2, IL-4, IL-5, and IL-10 responses than those treated as outpatients ( P = .02). </li></ul>Infants hospitalized for RSV infection:
  10. 10. Cytokine responses in cord blood predict the severity of later respiratory syncytial virus infection Juntti JACI 2009;124:52 2.20 High IL-6 and IL-8 responsiveness OR FOR SEVERE BRONCHIOLITIS 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0 P=0.01 <ul><li>cord blood samples from 1084 newborns (birth cohort) </li></ul><ul><li>47 of these newborns with RSV infection before 6 months of age. </li></ul>
  11. 11. Cytokine responses in cord blood predict the severity of later respiratory syncytial virus infection Juntti JACI 2009;124:52 2.20 High IL-6 and IL-8 responsiveness OR FOR SEVERE BRONCHIOLITIS 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0 P=0.01 <ul><li>cord blood samples from 1084 newborns (birth cohort) </li></ul><ul><li>47 of these newborns with RSV infection before 6 months of age. </li></ul>Natural differences in innate immunity predispose children to severe RSV infection rather than the infection modifying immune responses in childhood.
  12. 12. Surfactant protein A (SP-A) is now recognized as a pattern recognition receptor functioning as a component of the innate immune system . The human SP-A gene locus consists of 2 functional genes, SP-A1 and SP-A2. Both SP-A loci are polymorphic, with several single-nucleotide polymorphisms (SNPs) Surfactant Protein A2 Polymorphisms and Disease Severity in a Respiratory Syncytial Virus-Infected Population Saleeby J Pediatr 2010;156:409
  13. 13. 0.15 1.0 – 0.5 – 0 <ul><li>Infected children aged ≤ 24 months enrolled in 3 RSV seasons. </li></ul><ul><li>SP-A genotyping. </li></ul>OR for hospitalization in homozygote for 1A° allele Surfactant Protein A2 Polymorphisms and Disease Severity in a Respiratory Syncytial Virus-Infected Population Saleeby J Pediatr 2010;156:409 P=0.001
  14. 14. 2.15 <ul><li>Infected children aged ≤ 24 months enrolled in 3 RSV seasons. </li></ul><ul><li>SP-A genotyping. </li></ul>OR in subjects homozygous or heterozygous for an asparagine at amino acid position 9 Surfactant Protein A2 Polymorphisms and Disease Severity in a Respiratory Syncytial Virus-Infected Population Saleeby J Pediatr 2010;156:409 P=0.022 3 – 2 – 1 – 0 intensive care admission
  15. 15. Does Low Birth Weight Confer a Lifelong Respiratory Disadvantage? Greenough Am J Respir Crit Care Med 2009;180:107 <ul><li>Almost 20 years ago Barker reported that airway function was diminished in adults born with lower birth weight and speculated that prenatal nutrition might program fetal lung growth. </li></ul><ul><li>Subsequently, evidence has shown that low birth weight is associated with excess respiratory morbidity in adults, regardless of whether the low birth weight was the result of in utero growth retardation or premature birth. </li></ul>
  16. 16. Low Birth Weight and Respiratory Disease in Adulthood A Population-based Case-Control Study Walter Am J Respir Crit Care Med 2009;180:176 <ul><li>Rationale : The proportion of low and very low birth weight births is increasing. Infants and children with a history of low and very low birth weight have an increased risk of respiratory illnesses, but it is unknown if clinically significant disease persists into adulthood. </li></ul><ul><li>Objectives : To determine if a history of low birth weight is associated with hospitalization for respiratory illness in adulthood. </li></ul>
  17. 17. Low Birth Weight and Respiratory Disease in Adulthood A Population-based Case-Control Study Walter Am J Respir Crit Care Med 2009;180:176 <ul><li>Case-control study. </li></ul><ul><li>Cases adults 18 to 27 yrs hospitalized for a respiratory illness from 1998 to 2007 . </li></ul><ul><li>18,445 control subjects. </li></ul><1.500g OR FOR HOSPITALIZATION <1.500-2.499g >2.500g 1.83 1.34 1 p<0.0005 P=0.001 2.0 – 1.5 – 1.0 – 0.5 – 0 BIRTH WEIGHT
  18. 18. Low Birth Weight and Respiratory Disease in Adulthood A Population-based Case-Control Study Walter Am J Respir Crit Care Med 2009;180:176 <ul><li>Case-control study. </li></ul><ul><li>Cases adults 18 to 27 yrs hospitalized for a respiratory illness from 1998 to 2007 . </li></ul><ul><li>18,445 control subjects. </li></ul><1.500g OR FOR HOSPITALIZATION <1.500-2.499g >2.500g 1.83 1.34 1 p<0.0005 P=0.001 2.0 – 1.5 – 1.0 – 0.5 – 0 BIRTH WEIGHT Adults with a history of very low birth weight or moderately low birth weight were at increased risk of hospitalization for respiratory illness.
  19. 19. Relative Impact of Influenza and Respiratory Syncytial Virus in Young Children Bourgeois Pediatrics 2009;124:e1072 <ul><li>Patients who were aged ≤7 years and treated in the ED of a tertiary care pediatric hospital </li></ul><ul><li>2 winter seasons between 2003 and 2005. </li></ul>ED VISITS FOR 1000 CHILDREN 10.2 30 – 20 – 10 – 0 21.5 INFLUENZA RSV ATTRIBUTABLE TO
  20. 20. Relative Impact of Influenza and Respiratory Syncytial Virus in Young Children Bourgeois Pediatrics 2009;124:e1072 <ul><li>Patients who were aged ≤7 years and treated in the ED of a tertiary care pediatric hospital </li></ul><ul><li>2 winter seasons between 2003 and 2005. </li></ul>ED VISITS FOR 1000 CHILDREN 10.2 30 – 20 – 10 – 0 21.5 INFLUENZA RSV ATTRIBUTABLE TO Children who were aged 0 to 23 months and infected with RSV had the highest rate of ED visits with 64.4 visits per 1000 children.
  21. 21. Bronchiolitis Assesment
  22. 22. Inter-observer agreement between physicians, nurses, and respiratory therapists for respiratory clinical evaluation in bronchiolitis Gajdos, Ped Pul 2009;44:754 5/60 85% 51/60 <ul><li>82 physicians, nurses, and respiratory therapists aimed to evaluate inter-observer agreement for clinical evaluations in children hospitalized for a first episode of bronchiolitis. </li></ul>score
  23. 23. Inter-observer agreement between physicians, nurses, and respiratory therapists for respiratory clinical evaluation in bronchiolitis Gajdos, Ped Pul 2009;44:754 5/60 85% 51/60 <ul><li>82 physicians, nurses, and respiratory therapists aimed to evaluate inter-observer agreement for clinical evaluations in children hospitalized for a first episode of bronchiolitis. </li></ul>score Overall inter-observer agreement for all provider pairs was 93.1%.
  24. 24. <ul><li>a consecutive cohort of infants hospitalized with RSV from the available literature </li></ul><ul><li>5575 hospitalized patients with RSV </li></ul>Incidence of apnea 25 – 20 – 15 – 10 – 5 – 0 TERM Incidence of Apnea in Infants Hospitalized with Respiratory Syncytial Virus Bronchiolitis: A Systematic Review S Ralston, J Ped 2009;155;728 PRETERM 1.2% 23.8% INFANTS
  25. 25. <ul><li>a consecutive cohort of infants hospitalized with RSV from the available literature </li></ul><ul><li>5575 hospitalized patients with RSV </li></ul>Incidence of apnea 25 – 20 – 15 – 10 – 5 – 0 TERM Incidence of Apnea in Infants Hospitalized with Respiratory Syncytial Virus Bronchiolitis: A Systematic Review S Ralston, J Ped 2009;155;728 PRETERM 1.2% 23.8% INFANTS Recent studies have found a <1% incidence of apnea with RSV in previously healthy term infants
  26. 26. LDH Concentration in Nasal-Wash Fluid as a Biochemical Predictor of Bronchiolitis Severity Laham Pediatrics 2010;125:e225 OBJECTIVE: Because the decision to hospitalize an infant with bronchiolitis is often supported by subjective criteria and objective indicators of bronchiolitis severity are lacking, we tested the hypothesis that lactate dehydrogenase (LDH), which is released from injured cells , is a useful biochemical indicator of bronchiolitis severity.
  27. 27. LDH Concentration in Nasal-Wash Fluid as a Biochemical Predictor of Bronchiolitis Severity Laham Pediatrics 2010;125:e225 % Children with isolates 66% 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 19% RSV Rhinovirus <ul><li>Nasal wash (NW) </li></ul><ul><li>101 children (median age: 5.6 mo), 98 with brochiolitis </li></ul>
  28. 28. LDH Concentration in Nasal-Wash Fluid as a Biochemical Predictor of Bronchiolitis Severity Laham Pediatrics 2010;125:e225 Nasal wash LDH concentration, U/mL Values in the upper quartile were associated with ~80% risk reduction in hospitalization, likely reflecting a robust antiviral response. <ul><li>Nasal wash (NW) </li></ul><ul><li>101 children (median age: 5.6 mo), 98 with brochiolitis </li></ul>
  29. 29. LDH Concentration in Nasal-Wash Fluid as a Biochemical Predictor of Bronchiolitis Severity Laham Pediatrics 2010;125:e225 Nasal wash concentrations according to hospitalization status <ul><li>Nasal wash (NW) </li></ul><ul><li>101 children (median age: 5.6 mo), 98 with brochiolitis </li></ul>
  30. 30. LDH Concentration in Nasal-Wash Fluid as a Biochemical Predictor of Bronchiolitis Severity Laham Pediatrics 2010;125:e225 <ul><li>Nasal wash (NW) </li></ul><ul><li>101 children (median age: 5.6 months), 98 with brochiolitis </li></ul>Nasal wash concentrations according to hospitalization status NW LDH may be a useful biomarker to assist the clinician in the decision to hospitalize a child with bronchiolitis
  31. 31. BronchiolitisTreatment
  32. 32. Bronchiolitis: Recent Evidence on Diagnosis and Management Zorc Pediatrics 2010;125:342 Summary of Recent Evidence for Therapies Used for Bronchiolitis
  33. 33. Hypertonic saline or high volume normal saline for viral bronchiolitis: Mechanisms and rationale Mandelberg, Ped Pul 2010;45:36 <ul><li>Mucus clearance ( MC ). </li></ul><ul><li>Airway surface liquid ( ASL ). </li></ul><ul><li>MC failure is a dominant factor not only in CF but in most airway diseases. </li></ul><ul><li>Exacerbations in many airway diseases result from intermittent catastrophic failures of MC due to dehydration of ASL often triggered by viral infections . </li></ul><ul><li>Thus, therapy to maintain ASL hydration is probably important during viral exacerbations not only in CF patients but in all chronic airway diseases. </li></ul>
  34. 34. Hypertonic saline or high volume normal saline for viral bronchiolitis: Mechanisms and rationale Mandelberg, Ped Pul 2010;45:36 Efficient clearance requires the coordinated interaction of two separate layers: an overlying transported mucus layer (ML) and a separate, distinct environment near the cell surface called periciliary liquid (PCL).
  35. 35. Hypertonic saline or high volume normal saline for viral bronchiolitis: Mechanisms and rationale Mandelberg, Ped Pul 2010;45:36 Maintaining normal height of the PCL (around 7 ц m) is crucial for maintaining normal airway mucociliary clearance (MCC) so that the moving tips of the cilia will precisely contact the lower margin of the ML. periciliary liquid ≈ 7 ц m
  36. 36. Hypertonic saline or high volume normal saline for viral bronchiolitis: Mechanisms and rationale Mandelberg, Ped Pul 2010;45:36 Dehydration of the airway surface liquid occurs in response to a relatively mild RSV infection. The ML then donates water to preserve at least some Mucus clearance while maintaining the PCL height close to the normal approximately 7 ц m and resulting in Mucus layer dehydration. H 2 O
  37. 37. When this donor mechanism is exhausted, the ML has no more water to donate, the PCL may start to contract to the poin that MCC is impossible. Hypertonic saline or high volume normal saline for viral bronchiolitis: Mechanisms and rationale Mandelberg, Ped Pul 2010;45:36 H 2 O X
  38. 38. High volume normal saline alone is as effective as nebulized salbutamol-normal saline, epinephrine-normal saline, and 3% saline in mild bronchiolitis Anil, Ped Pul 2010;45:41 <ul><li>186 children (mean age 9.5 ± 5.3 months), with mild bronchiolitis. </li></ul><ul><li>4 ml dose either of : - 1.5 mg epinephrine plus normal saline or - 1.5 mg epinephrine plus 3% saline or - 2.5 mg salbutamol plus normal saline or - 2.5 mg salbutamol plus 3% saline or - normal saline alone at 0 and 30 min . </li></ul><ul><li>There were no significant differences between the outcome variables of the groups. </li></ul><ul><li>All treatment modalities used in this study, including a total of 8 ml normal saline inhalation at 30-min interval showed clinically significant and swift improvement in mildly affected ambulatory infants with acute bronchiolitis. </li></ul>
  39. 39. High volume normal saline alone is as effective as nebulized salbutamol-normal saline, epinephrine-normal saline, and 3% saline in mild bronchiolitis Anil, Ped Pul 2010;45:41 Clinical Severity Scores Wang E, Milner R, Navas J, Maj H. Observe agreement for respiratory signs and oxymetry in infants hospitalized with lower respiratory infections. Am Rev Respir Dis 1992;145:106–109.
  40. 40. <ul><li>3556 infants </li></ul><ul><li>800 infants randomised into four groups: nebulised epinephrine plus oral dexamethasone ( group 1 ); nebulised epinephrine plus oral placebo ( group 2 ); nebulised placebo plus oral dexamethasone ( group 3 ); and nebulised placebo plus oral placebo ( group 4 ). </li></ul><ul><li>Combining epinephrine and dexamethasone led to a reduction in the rate of hospital admissions of 35%. </li></ul><ul><li>Infants in group 1 had lower respiratory rates and lower respiratory distress assessment index scores during the first hour of the study, were discharged earlier from medical care and appeared to return to quiet breathing and normal or almost normal feeding more quickly (secondary outcomes) than those in the placebo group. </li></ul>Epinephrine and dexamethasone in children with bronchiolitis. Plint N Engl J Med 2009;360:2079–89.
  41. 41. Effect of dexamethasone on respiratory syncytial virus-induced lung inflammation in children: results of a randomized, placebo controlled clinical trial Somers Pediatr Allergy Immunol 2009:20:477 <ul><li>The effect of i.v. dexamethasone on cytokine concentrations in tracheal aspirates (TA) of children with severe RSV disease and to correlate them with disease severity. </li></ul><ul><li>i.v. dexamethasone (0.5 mg/kg; n = 22) vs. placebo (n = 19). </li></ul><ul><li>Systemic administration of dexamethasone did not have a consistent effect on concentrations of pro-inflammatory cytokines . </li></ul><ul><li>This may help explain, at least in part, the lack of clinical benefit of steroid treatment in children with severe RSV bronchiolitis . </li></ul>
  42. 42. Epinephrine and Dexamethasone in Children with Bronchiolitis Amy C. Plint, N Engl J Med 2009;360:2079 <ul><li>a multicenter, double-blind, placebo-controlled trial in which 800 infants (6 weeks to 12 months of age) with bronchiolitis who were seen in the pediatric emergency department were randomly assigned to one of four study groups. </li></ul><ul><li>One group received two treatments of nebulized epinephrine (3 ml of epinephrine in a 1:1000 solution per treatment) and a total of six oral doses of dexamethasone (1.0 mg per kilogram of body weight in the emergency department and 0.6 mg per kilogram for an additional 5 days) (the epinephrine–dexamethasone group ), </li></ul><ul><li>the second group received nebulized epinephrine and oral placebo (the epinephrine group ), </li></ul><ul><li>the third received nebulized placebo and oral dexamethasone (the dexamethasone group ), </li></ul><ul><li>the fourth received nebulized placebo and oral placebo (the placebo group ). </li></ul><ul><li>The primary outcome was hospital admission within 7 days after the day of enrollment (the initial visit to the emergency department). </li></ul>
  43. 43. Epinephrine and Dexamethasone in Children with Bronchiolitis Amy C. Plint, N Engl J Med 2009;360:2079 Frequency and Relative Risk of Hospital Admission on the Day of the Initial Emergency Department Visit, by Day 7, and by Day 22.
  44. 44. Epinephrine and Dexamethasone in Children with Bronchiolitis Amy C. Plint, N Engl J Med 2009;360:2079 Cumulative Admissions during the First 7 Days after the Initial Emergency Department Visit, According to Study Group. Enrollment data represent all patients admitted at their initial visit to the Emergency department, and data for day 1 represent patients admitted within 24 hours of this visit.
  45. 45. % pts admitted to the hospital by day 7 30 – 20 – 10 – 0 P=0.02 RR = 0.65 26.4% 25.6% 23.7% 17.1% epinephrine–dexamethasone epinephrine group dexamethasone group placebo group Epinephrine and Dexamethasone in Children with Bronchiolitis Amy C. Plint, N Engl J Med 2009;360:2079
  46. 46. Epinephrine and Dexamethasone in Children with Bronchiolitis Amy C. Plint, N Engl J Med 2009;360:2079 Median Days to Symptom Resolution, with Ratio to Placebo Value.
  47. 47. Epinephrine and Dexamethasone in Children with Bronchiolitis Amy C. Plint, N Engl J Med 2009;360:2079 <ul><li>We found an unexpected synergism between epinephrine and </li></ul><ul><li>dexamethasone. </li></ul><ul><li>Combined therapy with epinephrine and dexamethasone, as compared with placebo, appeared to reduce the rate of hospital admission in the 7 days after study enrollment by 9% points, with a relative risk reduction of 35%. </li></ul><ul><li>These results were not modified by RSV status, presence or absence of a history of atopy, or the severity or the duration of illness. </li></ul>
  48. 48. Given the small effect size of the study — 11 infants would have to be treated to prevent one hospital admission — it does not seem practical to apply the treatment, especially considering the potential effects of high-dose corticosteroids on brain and lung development in such young children. What is the best way to treat wheezing in a preschooler? The Challenge of Managing Wheezing in Infants Editorial Urs Frey N Engl J Med 2009;360:2130
  49. 49. “… Although it is essential during the first episode to provide supportive care — including supplemental oxygen, hydration, nutrition, and short-term bronchodilation — the key intervention is close follow-up . We need to assess risk factors and symptom history and make sure that we identify and treat children with unremitting wheezing. In these children, particularly those presenting with signs of atopy, maintenance treatment can be initiated with inhaled corticosteroids , administered through an appropriate spacer, or with leukotriene-receptor antagonists.” The Challenge of Managing Wheezing in Infants Editorial Urs Frey N Engl J Med 2009;360:2130
  50. 50. <ul><li>44 children aged 3–24 months with acute bronchiolitis, still requiring oxygen supplementation 24 h after admission to hospital </li></ul><ul><li>oxygen supplementation at home with support from ‘‘hospital in the home’’ (HiTH) or to continue oxygen supplementation in hospital. </li></ul>HOME OXYGEN FOR CHILDREN WITH ACUTE BRONCHIOLITIS Tie Arch Dis Child 2009;94:641 Hours in hospital 100 – 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 55.2h HiTH 96.9h CONTROLS
  51. 51. <ul><li>44 children aged 3–24 months with acute bronchiolitis, still requiring oxygen supplementation 24 h after admission to hospital </li></ul><ul><li>oxygen supplementation at home with support from ‘‘hospital in the home’’ (HiTH) or to continue oxygen supplementation in hospital. </li></ul>HOME OXYGEN FOR CHILDREN WITH ACUTE BRONCHIOLITIS Tie Arch Dis Child 2009;94:641 Hours in hospital 100 – 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 55.2h HiTH 96.9h CONTROLS Children in the HiTH group spent almost 2 days less in a hospital bed
  52. 52. HOME OXYGEN FOR CHILDREN WITH ACUTE BRONCHIOLITIS Tie Arch Dis Child 2009;94:641
  53. 53. HOME OXYGEN FOR CHILDREN WITH ACUTE BRONCHIOLITIS Tie Arch Dis Child 2009;94:641 <ul><li>‘‘ safety in air test’’, designed to provide some degree of reassurance that if oxygen supplementation were interrupted for an extended period the child would not develop sudden, life-threatening hypoxia. The test involved continuous monitoring of pulse oxygen saturation (SpO 2 ) levels and clinical status of the child, while in room air, over a period of 20 minutes. If SpO 2 remained at ≥ 80% the child was considered to pass the test. </li></ul>
  54. 54. Bronchiolitis Long-term consequences
  55. 55. Exploring the Association between Severe Respiratory Syncytial Virus Infection and Asthma. A Registry-based Twin Study Thomsen Am J Respir Crit Care Med 2009;179:1091 <ul><li>All twins born in Denmark between 1994 and 2000 (8,280 pairs). </li></ul><ul><li>Information on asthma obtained from hospital discharge registries and parent-completed questionnaires. </li></ul>RSV hospitalization and asthma were positively associated ( r =0.43), and genetic determinants for the two disorders overlapped completely.
  56. 56. Exploring the Association between Severe Respiratory Syncytial Virus Infection and Asthma. A Registry-based Twin Study Thomsen Am J Respir Crit Care Med 2009;179:1091 <ul><li>All twins born in Denmark between 1994 and 2000 (8,280 pairs). </li></ul><ul><li>Information on asthma obtained from hospital discharge registries and parent-completed questionnaires. </li></ul>A model in which asthma &quot;causes&quot; RSV hospitalization fitted the data significantly better than a model in which RSV hospitalization &quot;causes&quot; asthma ( P <0.001).
  57. 57. Exploring the Association between Severe Respiratory Syncytial Virus Infection and Asthma. A Registry-based Twin Study Thomsen Am J Respir Crit Care Med 2009;179:1091 <ul><li>All twins born in Denmark between 1994 and 2000 (8,280 pairs). </li></ul><ul><li>Information on asthma obtained from hospital discharge registries and parent-completed questionnaires. </li></ul>A model in which asthma &quot;causes&quot; RSV hospitalization fitted the data significantly better than a model in which RSV hospitalization &quot;causes&quot; asthma ( P <0.001). RSV infection that is severe enough to warrant hospitalization does not cause asthma but is an indicator of the genetic predisposition to asthma.
  58. 58. Eosinophil activity in infants hospitalized for wheezing and risk of persistent childhood asthma Hyvärinen Pediatr Allergy Immunol 2010:21:96 % Children with Persistent Childhood Asthma (PCA) 25% 30 – 25 – 20 – 15 – 10 – 0 5 – 0 <ul><li>Blood eosinophil count (B-EOS), eosinophil cationic protein in serum (S-ECP) or in nasopharyngeal aspirate (NPA-ECP). </li></ul><ul><li>1992–1993, 100 infants aged <24 months were hospitalized for wheezing associated with respiratory infection. </li></ul><ul><li>Follow-up 4-12 yrs. </li></ul>
  59. 59. Eosinophil activity in infants hospitalized for wheezing and risk of persistent childhood asthma Hyvärinen Pediatr Allergy Immunol 2010:21:96 <ul><li>Blood eosinophil count (B-EOS), eosinophil cationic protein in serum (S-ECP) or in nasopharyngeal aspirate (NPA-ECP). </li></ul><ul><li>1992–1993, 100 infants aged <24 months were hospitalized for wheezing associated with respiratory infection. </li></ul><ul><li>Follow-up 4-12 yrs. </li></ul>Fold Increase for Persistent Childhood Asthma (PCA) in Children with B-EOS  ≥ 0.450×10 9   cells/l 2.9 6.1 6.7 S-ECP ≥20.0 μg/l NPA-ECP ≥815.0 ng/g 10 – 9 – 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0
  60. 60. Eosinophil activity in infants hospitalized for wheezing and risk of persistent childhood asthma Hyvärinen Pediatr Allergy Immunol 2010:21:96 Blood eosinophils (B-EOS), serum eosinophil cationic protein (S-ECP) and nasopharyngeal ECP (NPA-ECP) measured during acute wheezing in infancy, in relation to Persistent Childhood Asthma (PCA) .
  61. 61. Recurrent wheezing after respiratory syncytial virus or non-respiratory syncytial virus bronchiolitis in infancy: a 3-year follow-up. Valkonen Allergy 2009:64:1359 Background:  Recent studies have suggested that rhinovirus -associated early wheezing is a greater risk factor for development of recurrent wheezing in children than is early wheezing associated with respiratory syncytial virus (RSV). We determined the development of recurrent wheezing in young children within 3 years after hospitalization for RSV or non-RSV bronchiolitis.
  62. 62. Recurrent wheezing after respiratory syncytial virus or non-respiratory syncytial virus bronchiolitis in infancy: a 3-year follow-up. Valkonen Allergy 2009:64:1359 <ul><li>All children <2 years of age admitted because of bronchiolitis. </li></ul><ul><li>Nasopharyngeal aspirates for viral antigens for RSV, influenza A and B viruses, parainfluenza types 1, 2, and 3 viruses, and adenovirus. </li></ul>The age distribution of children hospitalized with RSV or non-RSV bronchiolitis
  63. 63. Recurrent wheezing after respiratory syncytial virus or non-respiratory syncytial virus bronchiolitis in infancy: a 3-year follow-up. Valkonen Allergy 2009:64:1359 <ul><li>All children <2 years of age admitted because of bronchiolitis. </li></ul><ul><li>Nasopharyngeal aspirates for viral antigens for RSV, influenza A and B viruses, parainfluenza types 1, 2, and 3 viruses, and adenovirus. </li></ul>Development of recurrent wheezing within 3 years
  64. 64. Recurrent wheezing after respiratory syncytial virus or non-respiratory syncytial virus bronchiolitis in infancy: a 3-year follow-up. Valkonen Allergy 2009:64:1359 <ul><li>All children <2 years of age admitted because of bronchiolitis. </li></ul><ul><li>Nasopharyngeal aspirates for viral antigens for RSV, influenza A and B viruses, parainfluenza types 1, 2, and 3 viruses, and adenovirus. </li></ul>Children hospitalized with bronchiolitis caused by other viruses than RSV develop recurrent wheezing at substantially higher rates during a 3-year follow-up period Development of recurrent wheezing within 3 years
  65. 65. 50% 70% YES NO School age outcome of hospitalisation with respiratory syncytial virus infection of prematurely born infants Greenough, Thorax 2009 64: 490-495 <ul><li>Children hospitalised with RSV infection (n=14); </li></ul><ul><li>Children hospitalised for non-RSV causes (n=63). </li></ul>FEF 50 (% pred) at age 8-10 yrs 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 p=0.03 RSV
  66. 66. School age outcome of hospitalisation with respiratory syncytial virus infection of prematurely born infants Greenough, Thorax 2009 64: 490-495 50% 70% YES NO <ul><li>Children hospitalised with RSV infection (n=14); </li></ul><ul><li>Children hospitalised for non-RSV causes (n=63). </li></ul>FEF 50 (% pred) at age 8-10 yrs 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 p=0.03 RSV In prematurely born children who had BPD, hospitalisation due to RSV infection in the first 2 years is associated with reduced airway calibre at school age.
  67. 67. Pediatric obstructive sleep apnea: A potential late consequence of respiratory syncitial virus bronchiolitis Ayelet Snow Ped Pul 2009;44:1186 <ul><li>21 children (mean age 5.2  years) with RSV- bronchiolitis during their first year of life </li></ul><ul><li>Overnight sleep study (NPSG). </li></ul><ul><li>Children recruited from the general population with no history of RSV bronchiolitis served as a control group. </li></ul>3 – 2 – 1 – 0 2.3 0.6 RSV bronchiolitis Controls OBSTRUCTIVE APNEA/HYPOPNEA INDEX p <0.05
  68. 68. Pediatric obstructive sleep apnea: A potential late consequence of respiratory syncitial virus bronchiolitis Ayelet Snow PP 2009;44:1186 1.3 RSV bronchiolitis Controls p <0.05 1.3 – 1.2 – 1.1 - 1.0 – 0.9 – 0.8 – 0.7 – 0.6 – 0.5 – 0.4 – 0.3 – 0.2 – 0.1 – 0 0.1 RESPIRATORY AROUSAL INDICES <ul><li>21 children (mean age 5.2  years) with RSV- bronchiolitis during their first year of life </li></ul><ul><li>Overnight sleep study (NPSG). </li></ul><ul><li>Children recruited from the general population with no history of RSV bronchiolitis served as a control group. </li></ul>
  69. 69. Pediatric obstructive sleep apnea: A potential late consequence of respiratory syncitial virus bronchiolitis Ayelet Snow PP 2009;44:1186 <ul><li>Awakenings were defined as sustained arousal lasting for ≥ 15 sec. </li></ul><ul><li>Arousals were expressed as the total number of arousals </li></ul><ul><li>per hour of TST (arousal index). </li></ul><ul><li>The apnea index was defined as the number of episodes of apnea per hour of the total sleep time (TST). </li></ul><ul><li>Obstructive apnea was defined as the absence of airflow with continued chest wall and abdominal movements for the duration of at least 2 breaths. </li></ul><ul><li>The obstructive apnea/hypopnea index (AHI) was defined as </li></ul><ul><li>the number of episodes of obstructive apnea and hypopnea </li></ul><ul><li>per hour of TST. </li></ul>      TO P      ABSTRACT     ME THODS     RE SULTS     DI SCUSSION     Su pport statement     St atement of interest     AC KNOWLEDGEMENTS     RE FERENCES      TO P      ABSTRACT     ME THODS     RE SULTS     DI SCUSSION     Su pport statement     St atement of interest     AC KNOWLEDGEMENTS     RE FERENCES
  70. 70. <ul><li>Esiste uno score clinico che può essere utilizzato anche dal personale paramedico, </li></ul><ul><li>Attenti all’apnea soprattutto nel prematuro, </li></ul><ul><li>È chiaro perché funziona l’ipertonica ma anche la soluzione fisiologica, </li></ul><ul><li>Alcuni bambini possono continuare l’ossigeno-terapia a domicilio ma con una buona organizzazione dei servizi, </li></ul><ul><li>L’eosinofilia e l’eziologia da rinovirus sono predittivi di possibile problema persistente. </li></ul>
  71. 71. <ul><li>cough </li></ul>
  72. 72. The online Cough Clinic: developing guideline-based diagnosis and advice . Dettmar ERJ 2009:34:819 <ul><li>8,546 adults with chronic cough completed the Cough Clinic diagnostic questionnaire. </li></ul><ul><li>Response to 16 specific questions. </li></ul>
  73. 73. <ul><li>Cough with eating (during or straight after meals) Reflux </li></ul><ul><li>Cough with certain foods Reflux </li></ul><ul><li>Cough when you get out of bed in the morning Reflux </li></ul><ul><li>Cough brought on by singing or speaking (for example, on the telephone) Reflux </li></ul><ul><li>Hoarseness or a problem with your voice Reflux </li></ul><ul><li>Clearing your throat Reflux </li></ul><ul><li>Cough after lying down Reflux </li></ul><ul><li>Heartburn, chest pain, indigestion or stomach acid coming up Reflux </li></ul>Questions used to ascertain the probable medical condition responsible for a patient's chronic cough N° Question Weighting The online Cough Clinic: developing guideline-based diagnosis and advice . Dettmar ERJ 2009:34:819
  74. 74. <ul><li>Wheezing or chest tightness in general Asthma </li></ul><ul><li>Cough waking you from sleep Asthma </li></ul><ul><li>Shortness of breath when not coughing Asthma </li></ul><ul><li>Blocked or stuffy nose Rhinitis </li></ul><ul><li>Excess mucus in the throat, or dripping down the back of the nose Rhinitis </li></ul><ul><li>Itchy nose and/or sneezing Rhinitis </li></ul><ul><li>Loss of the sense of smell Rhinitis </li></ul><ul><li>A feeling that mucus is running down the back of your throat Rhinitis </li></ul>N° Question Weighting The severity of the above key diagnostic symptoms was rated on a Likert scale (0–5). The questions were asked in a random order and not as listed. The online Cough Clinic: developing guideline-based diagnosis and advice . Dettmar ERJ 2009:34:819 Questions used to ascertain the probable medical condition responsible for a patient's chronic cough
  75. 75. Breakdown of ages of the population completing the questionnaire. There was no specific dominant age group. Probable diagnosis of medical condition responsible for chronic cough in 8,546 patients completing the Cough Clinic questionnaire. The online Cough Clinic: developing guideline-based diagnosis and advice . Dettmar ERJ 2009:34:819
  76. 76. Cough in the Pediatric Population Goldsobel J Pediatr 2010;156:352
  77. 77. Cough in the Pediatric Population Goldsobel J Pediatr 2010;156:352 Algorithm for evaluating chronic cough in children
  78. 78. Cough in the Pediatric Population Goldsobel J Pediatr 2010;156:352 Algorithm for evaluating specific chronic cough in children
  79. 79. <ul><li>40 children </li></ul><ul><li>(age range, </li></ul><ul><li>5 to 12 years) </li></ul><ul><li>with chronic cough </li></ul><ul><li>(> 8 weeks duration) </li></ul><ul><li>with no obvious cause </li></ul><ul><li>who were referred by their primary care physicians. </li></ul>% children 27.5% asthma 20% Multiple etiologies Associated Factors in Children With Chronic Cough Khoshoo Chest 2009;136:811 5% aspiration 30 – 20 – 10 – 0 2.5% 22.5% 12.5% allergy GER infection
  80. 80. <ul><li>40 children </li></ul><ul><li>(age range, </li></ul><ul><li>5 to 12 years) </li></ul><ul><li>with chronic cough </li></ul><ul><li>(> 8 weeks duration) </li></ul><ul><li>with no obvious cause </li></ul><ul><li>who were referred by their primary care physicians. </li></ul>% children 27.5% asthma 20% Multiple etiologies Associated Factors in Children With Chronic Cough Khoshoo Chest 2009;136:811 5% aspiration 30 – 20 – 10 – 0 2.5% 22.5% 12.5% allergy GER infection Reflux, allergy, and asthma accounted for > 80% of the likely etiologic factors of chronic cough in children and responded to appropriate treatment.
  81. 81. Background: Chronic cough is common, and medical treatment can be ineffective. Mindfulness is a psychological intervention that aims to teach moment-to-moment non-judgemental awareness of thoughts, feelings and sensations and has proven effective in the management of several chronic disease states including chronic pain, depression, fibromyalgia and psoriasis. Mindfulness training is classically led by experts and practised in group sessions over an 8- to 10-week period with regular homework activities to encourage integration of the coping strategies into everyday life. The effect of mindfulness meditation on cough reflex sensitivity Young Thorax 2009; 64: 993-998
  82. 82. <ul><li>30 healthy subjects and 30 patients with chronic cough; </li></ul><ul><li>Cough reflex sensitivity to citric acid (C5) with urge to cough rated following each inhalation; </li></ul><ul><li>Randomised to </li></ul><ul><li>( 1 ) no intervention, ( 2 ) mindfulness or ( 3 ) no intervention but modified cough challenge (subjects suppress coughing). </li></ul>Changes in cough reflex sensitivity to citric acid in healthy volunteers for the control, mindfulness intervention and voluntary cough suppression groups. The effect of mindfulness meditation on cough reflex sensitivity Young Thorax 2009; 64: 993-998
  83. 83. <ul><li>30 healthy subjects and 30 patients with chronic cough; </li></ul><ul><li>Cough reflex sensitivity to citric acid (C5) with urge to cough rated following each inhalation; </li></ul><ul><li>Randomised to </li></ul><ul><li>( 1 ) no intervention, ( 2 ) mindfulness or ( 3 ) no intervention but modified cough challenge (subjects suppress coughing). </li></ul>Changes in urge to cough at the citric acid cough threshold (C5) in healthy volunteers for the control, mindfulness intervention and voluntary cough suppression groups. The effect of mindfulness meditation on cough reflex sensitivity Young Thorax 2009; 64: 993-998
  84. 84. <ul><li>30 healthy subjects and 30 patients with chronic cough; </li></ul><ul><li>Cough reflex sensitivity to citric acid (C5) with urge to cough rated following each inhalation; </li></ul><ul><li>Randomised to </li></ul><ul><li>( 1 ) no intervention, ( 2 ) mindfulness or ( 3 ) no intervention but modified cough challenge (subjects suppress coughing). </li></ul>Changes in cough reflex sensitivity to citric acid in patients with chronic cough for the control, mindfulness intervention and voluntary cough suppression groups. The effect of mindfulness meditation on cough reflex sensitivity Young Thorax 2009; 64: 993-998
  85. 85. <ul><li>30 healthy subjects and 30 patients with chronic cough; </li></ul><ul><li>Cough reflex sensitivity to citric acid (C5) with urge to cough rated following each inhalation; </li></ul><ul><li>Randomised to </li></ul><ul><li>( 1 ) no intervention, ( 2 ) mindfulness or ( 3 ) no intervention but modified cough challenge (subjects suppress coughing). </li></ul>Changes in urge to cough at the citric acid cough threshold (C5) in patients with chronic cough for the control, mindfulness intervention and voluntary cough suppression groups. The effect of mindfulness meditation on cough reflex sensitivity Young Thorax 2009; 64: 993-998
  86. 86. Changes in urge to cough at the citric acid cough threshold (C5) in patients with chronic cough for the control, mindfulness intervention and voluntary cough suppression groups. <ul><li>30 healthy subjects and 30 patients with chronic cough; </li></ul><ul><li>Cough reflex sensitivity to citric acid (C5) with urge to cough rated following each inhalation; </li></ul><ul><li>Randomised to </li></ul><ul><li>(1) no intervention, (2) mindfulness or (3) no intervention but modified cough challenge (subjects suppress coughing). </li></ul>Compared with control, mindfulness decreased cough reflex sensitivity in healthy volunteers, but did not alter cough threshold in patients with chronic cough. Both groups were able to suppress cough responses to citric acid inhalation . The effect of mindfulness meditation on cough reflex sensitivity Young Thorax 2009; 64: 993-998
  87. 87. Pnumonia
  88. 88. Pnumonia Risk factors
  89. 89. Long-Term Exposure to Ambient Air Pollution and Risk of Hospitalization with Community-acquired Pneumonia in Older Adults Neupane AJRCCM 2009:181:47 NO 2 2.3 2.26 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0 PM 2.5 <ul><li>345 patients aged ≥ 65 years hospitalized for community-acquired pneumonia. </li></ul><ul><li>494 controls. </li></ul><ul><li>Levels of nitrogen dioxide, sulfur dioxide, and PM2.5 before the study period at the residential addresses of participants. </li></ul>p=0.012 LONG-TERM EXPOSURE TO HIGHER LEVELS OR for Hospitalization for Pneumonia 2.3 p=0.007
  90. 90. <ul><li>Serum 25 hydroxyvitamin D [25(OH)D] levels. </li></ul><ul><li>Young children with bronchiolitis (n = 55) or pneumonia (n = 50). (ALRI) </li></ul><ul><li>Subjects without respiratory symptoms (n = 92). </li></ul>Vitamin D deficiency in young children with severe acute lower respiratory infection McNally, Ped Pul 2009;44:981
  91. 91. Vitamin D deficiency in young children with severe acute lower respiratory infection McNally, Ped Pul 2009;44:981 <ul><li>Serum 25 hydroxyvitamin D [25(OH)D] levels. </li></ul><ul><li>Young children with bronchiolitis (n = 55) or pneumonia (n = 50). (ALRI) </li></ul><ul><li>Subjects without respiratory symptoms (n = 92). </li></ul>The mean vitamin D level for the entire ALRI group was not significantly different from the control group (81 ± 40 vs. 83 ± 30 nmol/L, respectively).
  92. 92. Vitamin D deficiency in young children with severe acute lower respiratory infection McNally, Ped Pul 2009;44:981 <ul><li>Serum 25 hydroxyvitamin D [25(OH)D] levels. </li></ul><ul><li>Young children with bronchiolitis (n = 55) or pneumonia (n = 50). (ALRI) </li></ul><ul><li>Subjects without respiratory symptoms (n = 92). </li></ul>87 49 P=0.001
  93. 93. Vitamin D deficiency in young children with severe acute lower respiratory infection McNally, Ped Pul 2009;44:981 <ul><li>Serum 25 hydroxyvitamin D [25(OH)D] levels. </li></ul><ul><li>Young children with bronchiolitis (n = 55) or pneumonia (n = 50). (ALRI) </li></ul><ul><li>Subjects without respiratory symptoms (n = 92). </li></ul>The mean vitamin D level for the ALRI subjects admitted to the pediatric intensive care unit (49 ± 24 nmol/L) was significantly lower (p=0.001) than that observed for both control (83 ± 30 nmol/L) and ALRI subjects admitted to the general pediatrics ward (87 ± 39 nmol/L). P=0.001 87 49
  94. 94. Vitamin D deficiency in young children with severe acute lower respiratory infection McNally, Ped Pul 2009;44:981 <ul><li>Serum 25 hydroxyvitamin D [25(OH)D] levels. </li></ul><ul><li>Young children with bronchiolitis (n = 55) or pneumonia (n = 50). (ALRI) </li></ul><ul><li>Subjects without respiratory symptoms (n = 92). </li></ul>P=0.001 Vitamin D deficiency (<50 nmol/L) remained associated with ALRI requiring admission to pediatric intensive care unit after the inclusion of prematurity into a multivariate logistic regression model. 87 49
  95. 95. <ul><li>Vitamin D influences antimicrobial activity, inflammation, and coagulation partly by regulating calcium and phosphorous homeostasis and by acting on lymphocytes , neutrophils , macrophages , and respiratory epithelial cells through vitamin D receptors . </li></ul><ul><li>In addition, the activity of Toll-like receptor (TLR)-4, responsible for initiating the immune response through pathogen associated </li></ul><ul><li>molecular patterns, are modulated by vitamin D. </li></ul><ul><li>Vitamin D also stimulates the innate immune system through vitamin D receptor-dependent expression of antimicrobial peptides ( cathelicidin and defensins ) and regulation of TLR signaling. Human antimicrobial peptides synthesized and expressed by macrophages, </li></ul><ul><li>neutrophils, and respiratory epithelium have activity against bacteria and some respiratory viruses, including influenza and respiratory syncytial virus </li></ul>Vitamin D deficiency in young children with severe acute lower respiratory infection McNally, Ped Pul 2009;44:981
  96. 96. Nutritional rickets and vitamin D deficiency Association with the outcomes of childhood very severe pneumonia: A prospective cohort study Banajeh, Ped Pul 2009;44:1207 19.9 35.2 <ul><li>Prospective cohort study. </li></ul><ul><li>152 children aged 2-59 months with very severe pneumonia (VSP). </li></ul>50 – 40 – 30 – 20 – 10 – 0 37.2% 47.3% p=0.019 % circulatin neutrophils ≤ 30nmol/L >30nmol/L Vitamin D levels
  97. 97. Nutritional rickets and vitamin D deficiency Association with the outcomes of childhood very severe pneumonia: A prospective cohort study Banajeh, Ped Pul 2009;44:1207 19.9 35.2 <ul><li>Prospective cohort study. </li></ul><ul><li>152 children aged 2-59 months with very severe pneumonia (VSP). </li></ul>25 – 20 – 15 – 10 – 5 – 0 20.6% 6% p=0.031 % treatment failure Vitamin D levels ≤30nmol/L rachitic non-rachitic
  98. 98. 19.9 35.2 <ul><li>Prospective cohort study. </li></ul><ul><li>152 children aged 2-59 months with very severe pneumonia (VSP). </li></ul>85.9% 89.8% Day–5 Oxigen saturation ≤ 30nmol/L >30nmol/L 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 p=0.03 Vitamin D levels Nutritional rickets and vitamin D deficiency Association with the outcomes of childhood very severe pneumonia: A prospective cohort study Banajeh, Ped Pul 2009;44:1207
  99. 99. 19.9 35.2 <ul><li>Prospective cohort study. </li></ul><ul><li>152 children aged 2-59 months with very severe pneumonia (VSP). </li></ul>85.9% 89.8% Day–5 Oxigen saturation ≤ 30nmol/L >30nmol/L 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 p=0.03 Vitamin D levels Nutritional rickets and vitamin D deficiency Association with the outcomes of childhood very severe pneumonia: A prospective cohort study Banajeh, Ped Pul 2009;44:1207 Vitamin D deficiency significantly associated with treatment outcome and VDD significantly predict both reduced circulating PMNs, and Day-5 hypoxemia (SpO 2 %, <88%).
  100. 100. <ul><li>5420 LRTI-associated infant deaths in the United States during 1999 –2004 </li></ul>Risk Factors for Lower Respiratory Tract Infection Death Among Infants in the United States, 1999-2004 Singleton Pediatrics 2009;124;e768 40 – 30 – 20 – 10 – 0 1.2 1.21 2.3 32 18 GENDER MALE BIRTH WEIGHT <2500 MOTHER AGE <20 GESTATIONAL AGE <32 W APGAR SCORE <7 AT 5 MIN OR FOR DEATH
  101. 101. 2.4 UNMARIED MOTHER >3 SIBLING NO PRENATAL CARE MATERNAL ALCOOL MATERNAL TOBACCO OR FOR DEATH 5 – 4 – 3 – 2 – 1 – 0 2 4.7 1.9 2.1 Risk Factors for Lower Respiratory Tract Infection Death Among Infants in the United States, 1999-2004 Singleton Pediatrics 2009;124;e768
  102. 102. Severity of Pneumococcal Pneumonia Associated With Genomic Bacterial Load Rello Chest 2009;136:832 Background : There is a clinical need for more objective methods of identifying patients at risk for septic shock and poorer outcomes among those with community-acquired pneumonia (CAP). As viral load is useful in viral infections, we hypothesized that bacterial load may be associated with outcomes in patients with pneumococcal pneumonia.
  103. 103. 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 <ul><li>Quantification of Streptococcus pneumoniae DNA level by real-time polymerase chain reaction (rt-PCR) on whole-blood samples </li></ul><ul><li>353 patients </li></ul>OR in patients with positive S pneumoniae rt-PCR assay for 7.08 MORTALITY 7.96 MECHANICAL VENTILATION Severity of Pneumococcal Pneumonia Associated With Genomic Bacterial Load Rello Chest 2009;136:832 6.29 SHOCK
  104. 104. 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 <ul><li>Quantification of Streptococcus pneumoniae DNA level by real-time polymerase chain reaction (rt-PCR) on whole-blood samples </li></ul><ul><li>353 patients </li></ul>OR in patients with positive S pneumoniae rt-PCR assay for 7.08 MORTALITY 7.96 MECHANICAL VENTILATION Severity of Pneumococcal Pneumonia Associated With Genomic Bacterial Load Rello Chest 2009;136:832 6.29 SHOCK In patients with pneumococcal pneumonia, bacterial load is associated with the likelihood of death, the risk of septic shock, and the need for MV. High genomic bacterial load for S pneumoniae may be a useful tool for severity assessment .
  105. 105. Pnumonia Etiology atypical bacteria
  106. 106. 93.7% Impact of weather factors on Mycoplasma pneumoniae pneumonia D. Onozuka, Thorax 2009 64: 507-511 <ul><li>Data on cases of M . pneumoniae pneumonia and weather factors from 1999 to 2007; </li></ul><ul><li>13 056 M.pneumoniae pneumonia cases. </li></ul>% cases under 15 years of age 100 – 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0
  107. 107. +16.9% +4.1% for every 1°C increase in the average temperature for every 1% increase in relative humidity The weekly number of M pneumoniae pneumonia cases increased by 20 – 15 – 10 – 5 – 0 Impact of weather factors on Mycoplasma pneumoniae pneumonia Onozuka, Thorax 2009 64: 507-511 <ul><li>Data on cases of M . pneumoniae pneumonia and weather factors from 1999 to 2007; </li></ul><ul><li>13 056 M.pneumoniae pneumonia cases. </li></ul>
  108. 108. +16.9% +4.1% for every 1°C increase in the average temperature for every 1% increase in relative humidity The weekly number of M pneumoniae pneumonia cases increased by 20 – 15 – 10 – 5 – 0 Impact of weather factors on Mycoplasma pneumoniae pneumonia Onozuka, Thorax 2009 64: 507-511 <ul><li>Data on cases of M . pneumoniae pneumonia and weather factors from 1999 to 2007; </li></ul><ul><li>13 056 M.pneumoniae pneumonia cases. </li></ul>Cases of M pneumoniae pneumonia increased significantly with increased average temperature and relative humidity.
  109. 109. <ul><li>Epidemiological longitudinal study suggested that the survival and spread of M pneumoniae were highly favoured during the spring and early autumn season. </li></ul><ul><li>M pneumoniae pneumonia cases are likely to increase with climate change. </li></ul><ul><li>Data on cases of M . pneumoniae pneumonia and weather factors from 1999 to 2007; </li></ul><ul><li>13 056 M.pneumoniae pneumonia cases. </li></ul>Impact of weather factors on Mycoplasma pneumoniae pneumonia Onozuka, Thorax 2009 64: 507-511
  110. 110. Increased serum interleukin-5 and vascular endothelial growth factor in children with acute mycoplasma pneumonia and wheeze Ic Sun Choi Ped Pul 2009;44:423 <ul><li>58 patients with mycoplasma pneumonia (12 with wheeze, Group1 ; 46 without wheeze, Group 2 ). </li></ul><ul><li>36 patients of non-mycoplasma pneumonia ( Group 3 ). </li></ul>Serum interleukin (IL)-5 levels      TO P      ABSTRACT     ME THODS     RE SULTS     DI SCUSSION     Su pport statement     St atement of interest     AC KNOWLEDGEMENTS     RE FERENCES      TO P      ABSTRACT     ME THODS     RE SULTS     DI SCUSSION     Su pport statement     St atement of interest     AC KNOWLEDGEMENTS     RE FERENCES
  111. 111. <ul><li>58 patients with mycoplasma pneumonia (12 with wheeze, Group1 ; 46 without wheeze, Group 2 ). </li></ul><ul><li>36 patients of non-mycoplasma pneumonia ( Group 3 ). </li></ul>Increased serum interleukin-5 and vascular endothelial growth factor in children with acute mycoplasma pneumonia and wheeze Ic Sun Choi Ped Pul 2009;44:423 Serum vascular endothelial growth factor (VEGF) levels      TO P      ABSTRACT     ME THODS     RE SULTS     DI SCUSSION     Su pport statement     St atement of interest     AC KNOWLEDGEMENTS     RE FERENCES      TO P      ABSTRACT     ME THODS     RE SULTS     DI SCUSSION     Su pport statement     St atement of interest     AC KNOWLEDGEMENTS     RE FERENCES
  112. 112. <ul><li>58 patients with mycoplasma pneumonia (12 with wheeze, Group1 ; 46 without wheeze, Group 2 ). </li></ul><ul><li>36 patients of non-mycoplasma pneumonia ( Group 3 ). </li></ul>Increased serum interleukin-5 and vascular endothelial growth factor in children with acute mycoplasma pneumonia and wheeze Ic Sun Choi Ped Pul 2009;44:423 Serum vascular endothelial growth factor (VEGF) levels IL-5 and VEGF may play an important role in the occurrence of wheeze during acute mycoplasma pneumonia.      TO P      ABSTRACT     ME THODS     RE SULTS     DI SCUSSION     Su pport statement     St atement of interest     AC KNOWLEDGEMENTS     RE FERENCES      TO P      ABSTRACT     ME THODS     RE SULTS     DI SCUSSION     Su pport statement     St atement of interest     AC KNOWLEDGEMENTS     RE FERENCES
  113. 113. Clinical Predictors of Pneumonia Among Children With Wheezing Bonnie Pediatrics 2009; 124:1 <ul><li>526 children ≤21 years of age with wheezing on examination </li></ul><ul><li>Chest radiography performed because of possible pneumonia </li></ul>% PATIENTS WITH RADIOGRAPHIC PNEUMONIA 4.9 % 5 – 4 – 3 – 2 – 1 – 0
  114. 114. Clinical Predictors of Pneumonia Among Children With Wheezing Bonnie Pediatrics 2009; 124:1 OR FOR PNEUMONIA 1.39 OXIGEN SATURATION ≤92% FEVER AT HOME ABDOMINAL PAIN 5 – 4 – 3 – 2 – 1 – 0 3.06 1.92 2.85 TEMPERATURE IN THE ED ≥ 38°C
  115. 115. Pnumonia assesment
  116. 116. 130 ± <48 h 400 – 350 – 300 – 250 – 200 – 150 – 100 – 0 50 – 0 327 ± <ul><li>Adults with severe pneumococcal pneumonia. </li></ul><ul><li>32 patients were included; 13 patients had <48 h of evolution and 19 patients had been sick for >48 h. </li></ul>The impact of time on the systemic inflammatory response in pneumococcal pneumonia Calbo ERJ 2010;35:614 CPR Levels (pg/ml) ≥ 48 h P<0.001 85 131 Group
  117. 117. 6 ± <48 h 9 ± <ul><li>Adults with severe pneumococcal pneumonia. </li></ul><ul><li>32 patients were included; 13 patients had <48 h of evolution and 19 patients had been sick for >48 h. </li></ul>The impact of time on the systemic inflammatory response in pneumococcal pneumonia Calbo ERJ 2010;35:614 Fibrinogen mg/ml ≥ 48 h p=0.001 1.8 2 10 – 9 – 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 Group
  118. 118. Admission hypoglycaemia is associated with adverse outcome in community-acquired pneumonia Singanayagam ERJ 2009:34:932 <ul><li>1050 consecutive patients presenting with a primary diagnosis of CAP. </li></ul><ul><li>Patients were divided into two groups, hypoglycaemic (<4.4 mmol·L –1 or <79.0 mg·dL –1 ) and nonhypoglycaemic (≥4.4 mmol·L –1 or 79.0 mg·dL –1 ). </li></ul>5.4% 10 – 9 – 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 % PATIENTS WITH HYPOGLYCEMIA
  119. 119. Admission hypoglycaemia is associated with adverse outcome in community-acquired pneumonia Singanayagam ERJ 2009:34:932 5.4% OR in Hypoglycemia Patients for 30-day mortality Need for inotropic support Mechanical ventilation 2.25 3.38 2.9 4.0 – 3.5 – 3.0 – 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0
  120. 120. 89% 21% Aspirate Lavage Evaluation of the effect of diagnostic methodology on the reported incidence of ventilator-associated pneumonia Conway Thorax 2009 64: 516-522 <ul><li>Aspirate and lavage were compared using paired samples from 53 patients with suspected VAP. </li></ul>100 – 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 % cases considered affected by VAP P<0.0001
  121. 121. 89% 21% Aspirate Lavage Evaluation of the effect of diagnostic methodology on the reported incidence of ventilator-associated pneumonia Conway Thorax 2009 64: 516-522 <ul><li>Aspirate and lavage were compared using paired samples from 53 patients with suspected VAP. </li></ul>100 – 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 % cases considered affected by VAP P<0.0001 Changing from exclusive aspirate to lavage diagnosis would decrease reported pneumonia incidence by 76% and antibiotic use by 30%.
  122. 122. Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study Stolz ERJ 2009:34:1364 <ul><li>A procalcitonin level of <0.25 µg·L –1 suggested the absence of VAP and discontinuation of antibiotics was strongly encouraged. </li></ul><ul><li>A procalcitonin level between 0.25 and 0.5 µg·L –1 or a decrease by ≥ 80% compared with day 0 indicated that bacterial infection was unlikely and reduction or discontinuation of antibiotics was encouraged. </li></ul><ul><li>A procalcitonin level ≥ 0.5 µg·L –1 or decrease by <80% compared with day 0 was considered to indicate unresolved bacterial infection and reduction or discontinuation of antibiotics was discouraged. </li></ul><ul><li>A procalcitonin level of >1 µg·L –1 strongly suggested unresolved bacterial infection and antibiotic discontinuation was strongly discouraged. </li></ul>
  123. 123. Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study Stolz ERJ 2009:34:1364 <ul><li>101 patients with VAP were assigned to an antibiotic discontinuation strategy according to guidelines (control group) or to serum procalcitonin concentrations (procalcitonin group). </li></ul>Reduction in the Overall Duration of Antibiotic Therapy in the Procalcitonin Group 0 -10 – -20 – -30 – -27% p=0.038
  124. 124. Pnumonia treatment
  125. 125. <ul><li>Targeted treatment was associated with: </li></ul><ul><li>a slightly higher overall cost (€1657.00 vs €1617.20, p=0.28 ), </li></ul><ul><li>reduction in the incidence of adverse events (9% vs 18%, p=0.12) and </li></ul><ul><li>lower exposure to broad-spectrum antimicrobials (154.4 vs 183.3 defined daily doses per 100 patient days). </li></ul><ul><li>177 pts: 89 assigned to empirical treatment and 88 to targeted treatment on the basis of the results from antigen tests. </li></ul>Prospective, randomised study to compare empirical treatment versus targeted treatment on the basis of the urine antigen results in hospitalised patients with community-acquired pneumonia Falguera Thorax 2010;65:101
  126. 126. Prospective, randomised study to compare empirical treatment versus targeted treatment on the basis of the urine antigen results in hospitalised patients with community-acquired pneumonia Falguera Thorax 2010;65:101 <ul><li>Targeted treatment was associated with: </li></ul><ul><li>a slightly higher overall cost (€1657.00 vs €1617.20, p=0.28 ), </li></ul><ul><li>reduction in the incidence of adverse events (9% vs 18%, p=0.12) and </li></ul><ul><li>lower exposure to broad-spectrum antimicrobials (154.4 vs 183.3 defined daily doses per 100 patient days). </li></ul><ul><li>177 pts: 89 assigned to empirical treatment and 88 to targeted treatment on the basis of the results from antigen tests. </li></ul>No statistically significant differences in other outcome parameters were observed.
  127. 127. % pts with clinical relapse 12% 15 – 10 – 5 – 0 3% P=0.04 target empirical treatment <ul><li>177 pts: 89 assigned to empirical treatment and 88 to targeted treatment on the basis of the results from antigen tests. </li></ul>Prospective, randomised study to compare empirical treatment versus targeted treatment on the basis of the urine antigen results in hospitalised patients with community-acquired pneumonia Falguera Thorax 2010;65:101
  128. 128. Prospective, randomised study to compare empirical treatment versus targeted treatment on the basis of the urine antigen results in hospitalised patients with community-acquired pneumonia Falguera Thorax 2010;65:101 % pts with clinical relapse 12% 15 – 10 – 5 – 0 3% P=0.04 target empirical treatment <ul><li>177 pts: 89 assigned to empirical treatment and 88 to targeted treatment on the basis of the results from antigen tests. </li></ul>The routine implementation of urine antigen detection tests does not carry substantial outcome-related or economic benefits to hospitalised patients with community-acquired pneumonia.
  129. 129. Prospective randomised study to compare empirical treatment versus targeted treatment on the basis of the urine antigen results in hospitalised patients with community-acquired pneumonia. Editorial Mandell Thorax 2010;65:93 <ul><li>Number of potential aetiological agents: bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus), atypical organisms (Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella species) and viruses. </li></ul><ul><li>Streptococcus pneumoniae can be particularly difficult to diagnose. Its identification in sputum may simply represent colonisation and its isolation from blood is woefully insensitive. </li></ul><ul><li>The overall sensitivity of the pneumococcal urinary antigen test is <80%. The specificity in adult patients with CAP can exceed 95%. False positives have been seen in children with chronic respiratory disease colonised with S pneumoniae and in patients who had a prior episode within the previous 3 months. </li></ul>
  130. 130. <ul><li>One of the main issues in the treatment of CAP is whether empirical therapy or pathogen-directed therapy is better. </li></ul><ul><li>Arguments in favour of an empirical approach include: the aetiological pathogen is not known with certainty; there may be multiple pathogens in a particular patient; and combination treatment may provide a benefit in certain cases, while those in favour of a directed treatment approach include: less antibiotic selection pressure; may lessen antimicrobial resistance development; and lower costs. </li></ul>Prospective randomised study to compare empirical treatment versus targeted treatment on the basis of the urine antigen results in hospitalised patients with community-acquired pneumonia. Editorial Mandell Thorax 2010;65:93
  131. 131. <ul><li>One of the main issues in the treatment of CAP is whether empirical therapy or pathogen-directed therapy is better. </li></ul><ul><li>Arguments in favour of an empirical approach include: the aetiological pathogen is not known with certainty; there may be multiple pathogens in a particular patient; and combination treatment may provide a benefit in certain cases, while those in favour of a directed treatment approach include: less antibiotic selection pressure; may lessen antimicrobial resistance development; and lower costs. </li></ul>Prospective randomised study to compare empirical treatment versus targeted treatment on the basis of the urine antigen results in hospitalised patients with community-acquired pneumonia. Editorial Mandell Thorax 2010;65:93 For sicker patients in particular, the arguments in support of empirical treatment prevail.
  132. 132. <ul><li>One of the main issues in the treatment of CAP is whether empirical therapy or pathogen-directed therapy is better. </li></ul><ul><li>Arguments in favour of an empirical approach include: the aetiological pathogen is not known with certainty; there may be multiple pathogens in a particular patient; and combination treatment may provide a benefit in certain cases, while those in favour of a directed treatment approach include: less antibiotic selection pressure; may lessen antimicrobial resistance development; and lower costs. </li></ul>Prospective randomised study to compare empirical treatment versus targeted treatment on the basis of the urine antigen results in hospitalised patients with community-acquired pneumonia. Editorial Mandell Thorax 2010;65:93 For pneumococcal bacteraemia combination treatment, particularly with a β -lactam and a macrolide, results in better outcomes.
  133. 133. Antibiotic Resistance in Community-Acquired Pneumonia Caused by Streptococcus Pneumoniae, Methicillin- Resistant S taphylococcus aureus, and Acinetobacter baumannii Ho CHEST 2009; 136:1119 <ul><li>In Europe, penicillin nonsusceptibility rates in France are 58%, but only 11% in Austria and 6% in Germany </li></ul><ul><li>In Spain, the macrolide resistance rate is reported to range from 28 to 64% </li></ul>Drug resistence S. Pneumoniae (DRSP)
  134. 134. Antibiotic Resistance in Community-Acquired Pneumonia Caused by Streptococcus Pneumoniae, Methicillin- Resistant S taphylococcus aureus, and Acinetobacter baumannii Ho CHEST 2009; 136:1119 <ul><li>In Europe, penicillin nonsusceptibility rates in France are 58%, but only 11% in Austria and 6% in Germany </li></ul><ul><li>In Spain, the macrolide resistance rate is reported to range from 28 to 64% </li></ul>Drug resistence S. Pneumoniae (DRSP) Penicillin-intermediate or penicillin-resistant pneumococci are more likely than susceptible isolates to have resistance to macrolides
  135. 135. <ul><li>Currently, the newer fluoroquinolones remain active against >98% of the pneumococci, </li></ul><ul><li>Nonetheless, significant fluoroquinolone resistance rates ( >5%) have been found by local studies in Italy, </li></ul><ul><li>The use of the heptavalent pneumococcal conjugate vaccine (PCV-7, targeting serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) in the year 2000 for children was followed by a drastic reduction in the incidence of pneumococcal infections among both children and adults. Because PCV-7 serotypes are often penicillin and multidrug resistant. </li></ul>Antibiotic Resistance in Community-Acquired Pneumonia Caused by Streptococcus Pneumoniae, Methicillin- Resistant S taphylococcus aureus, and Acinetobacter baumannii Ho CHEST 2009; 136:1119 Drug resistence S. Pneumoniae (DRSP)
  136. 136. <ul><li>At the current level of penicillin resistance, the clinical outcome of pneumococcal pneumonia is not adversely affected when appropriate β -lactam agents ( eg, penicillin, ampicillin, amoxicillin, cefotaxime, and ceftriaxone) and doses are used. </li></ul><ul><li>Maintaining a serum concentration above the minimum inhibitory concentration (MIC) for 40% of the dosing intervals for β -lactam antibiotics are predictive of favorable outcomes. </li></ul>Antibiotic Resistance in Community-Acquired Pneumonia Caused by Streptococcus Pneumoniae, Methicillin- Resistant S taphylococcus aureus, and Acinetobacter baumannii Ho CHEST 2009; 136:1119 Clinical relevance of antibiotic resistance of S. Pneumoniae
  137. 137. <ul><li>There is no evidence of bacteriologic failure for pneumococcal pneumonia with cefotaxime or ceftriaxone . </li></ul><ul><li>In contrast, patients who were treated with cefuroxime and were infected with pneumococci with in vitro nonsusceptibility to cefuroxime experienced significantly higher mortality rates. </li></ul><ul><li>Pharmacokinetics-pharmacodynamics principles indicate that some oral cephalosporins, including cephalothin , cefaclor , cefixime , and ceftibuten , are likely to be ineffective for the treatment of penicillinresistant S pneumoniae. </li></ul>Antibiotic Resistance in Community-Acquired Pneumonia Caused by Streptococcus Pneumoniae, Methicillin- Resistant S taphylococcus aureus, and Acinetobacter baumannii Ho CHEST 2009; 136:1119 Clinical relevance of antibiotic resistance of S. Pneumoniae
  138. 138. <ul><li>Unlike penicillin resistance, the existing data suggest that resistance to macrolides and fluoroquinolones could lead to treatment failures. </li></ul><ul><li>The older fluoroquinolones, including ciprofloxacin and ofloxacin and levofloxacin , which are poorly active against pneumococci, should not be used for the treatment of suspected or confirmed pneumococcal infection in the respiratory tract. </li></ul><ul><li>No treatment failure of S pneumoniae infections has been reported to occur with moxifloxacin and gatifloxacin . </li></ul>Antibiotic Resistance in Community-Acquired Pneumonia Caused by Streptococcus Pneumoniae, Methicillin- Resistant S taphylococcus aureus, and Acinetobacter baumannii Ho CHEST 2009; 136:1119 Clinical relevance of antibiotic resistance of S. Pneumoniae
  139. 139. <ul><li>When a patient with mild CAP caused by S pneumoniae is initially treated with an antibiotic to which the organism is resistant, there is evidence of an increased risk of progression to serious disease. </li></ul><ul><li>Failures associated with the macrolides are increasing. </li></ul><ul><li>When S pneumoniae is established or strongly suspected as the causative pathogen, the preferred antimicrobial agents are penicillin G or amoxicillin. </li></ul><ul><li>Some investigators have advocated combination therapy with both a penicillin and a macrolide for critically ill patients with pneumococcal bacteremia, but the necessity of this beyond the initial 2 days and in patients with CAP of mild-to-moderate severity remains controversial. </li></ul>Treatment of S. Pneumoniae Antibiotic Resistance in Community-Acquired Pneumonia Caused by Streptococcus Pneumoniae, Methicillin- Resistant S taphylococcus aureus, and Acinetobacter baumannii Ho CHEST 2009; 136:1119
  140. 140. <ul><li>Patients with CA-MRSA infection most commonly present with skin and soft-tissue infections. </li></ul><ul><li>Occasionally CA-MRSA can manifest as a severe disease such as necrotizing fasciitis, endocarditis, sepsis syndrome, and necrotizing pneumonia are more common in winter, and occur in association with influenza and parainfluenza virus. </li></ul>Community-acquired methicillin-resistant S aureus (CA-MRSA) Antibiotic Resistance in Community-Acquired Pneumonia Caused by Streptococcus Pneumoniae, Methicillin- Resistant S taphylococcus aureus, and Acinetobacter baumannii Ho CHEST 2009; 136:1119
  141. 141. <ul><li>In 1999, S aureus carrying PVL was associated with a highly fatal form of pneumonia that is characterized by extensive lung necrosis. </li></ul><ul><li>Typical features of necrotizing pneumonia caused by PVL-positive S aureus include high fever ( > 39°C), rapid breathing (respiratory rate, > 40 breaths/min), hemoptysis, leukopenia, extensive pulmonary involvement, and rapid progression to ARDS. </li></ul>Unique Features of Panton-Valentine leukocidin PVL-Positive S aureus Pneumonia Antibiotic Resistance in Community-Acquired Pneumonia Caused by Streptococcus Pneumoniae, Methicillin- Resistant S taphylococcus aureus, and Acinetobacter baumannii Ho CHEST 2009; 136:1119
  142. 142. <ul><li>In 1999, S aureus carrying PVL was associated with a highly fatal form of pneumonia that is characterized by extensive lung necrosis. </li></ul><ul><li>Typical features of necrotizing pneumonia caused by PVL-positive S aureus include high fever ( > 39°C), rapid breathing (respiratory rate, > 40 breaths/min), hemoptysis, leukopenia, extensive pulmonary involvement, and rapid progression to ARDS. </li></ul>Unique Features of Panton-Valentine leukocidin PVL-Positive S aureus Pneumonia Antibiotic Resistance in Community-Acquired Pneumonia Caused by Streptococcus Pneumoniae, Methicillin- Resistant S taphylococcus aureus, and Acinetobacter baumannii Ho CHEST 2009; 136:1119 Patients with the disease tend to be children and young adults with no underlying illness
  143. 143. <ul><li>In 1999, S aureus carrying PVL was associated with a highly fatal form of pneumonia that is characterized by extensive lung necrosis. </li></ul><ul><li>Typical features of necrotizing pneumonia caused by PVL-positive S aureus include high fever ( > 39°C), rapid breathing (respiratory rate, > 40 breaths/min), hemoptysis, leukopenia, extensive pulmonary involvement, and rapid progression to ARDS. </li></ul>Unique Features of Panton-Valentine leukocidin PVL-Positive S aureus Pneumonia Antibiotic Resistance in Community-Acquired Pneumonia Caused by Streptococcus Pneumoniae, Methicillin- Resistant S taphylococcus aureus, and Acinetobacter baumannii Ho CHEST 2009; 136:1119 Predictors of mortality included airway bleeding, erythroderma, and leukopenia
  144. 144. <ul><li>Because CA-MRSA is a rare cause of CAP in most communities, the routine incorporation of agents with anti-MRSA activity into empirical therapy cannot be justified. </li></ul><ul><li>However, a high index of suspicion for CA-MRSA pneumonia is required during the influenza season, especially in those young, healthy persons with rapidly progressive cavitary infiltrates and in those with a history of MRSA infection or close contact with an MRSA-infected person. </li></ul>Treatment of CA-MRSA Pneumonia Antibiotic Resistance in Community-Acquired Pneumonia Caused by Streptococcus Pneumoniae, Methicillin- Resistant S taphylococcus aureus, and Acinetobacter baumannii Ho CHEST 2009; 136:1119
  145. 145. <ul><li>In general, CA-MRSA is usually susceptible in vitro to vancomycin, linezolid, trimethoprim-sulfamethoxazole , rifampin, and tigecycline. CA-MRSA is sometimes susceptible to clindamycin, but the D-test has to be done to determine the presence of in vitro inducible resistance. </li></ul><ul><li>From 2003 to 2004, all of the CA-MRSA isolates were uniformly resistant to macrolides , and one-half of them were not susceptible to treatment with fluoroquinolones. </li></ul>Treatment of CA-MRSA Pneumonia Antibiotic Resistance in Community-Acquired Pneumonia Caused by Streptococcus Pneumoniae, Methicillin- Resistant S taphylococcus aureus, and Acinetobacter baumannii Ho CHEST 2009; 136:1119
  146. 146. <ul><li>In general, CA-MRSA is usually susceptible in vitro to vancomycin, linezolid, trimethoprim-sulfamethoxazole, rifampin, and tigecycline. CA-MRSA is sometimes susceptible to clindamycin, but the D-test has to be done to determine the presence of in vitro inducible resistance. </li></ul><ul><li>From 2003 to 2004, all of the CA-MRSA isolates were uniformly resistant to macrolides, and one-half of them were not susceptible to treatment with fluoroquinolones. </li></ul>Treatment of CA-MRSA Pneumonia Antibiotic Resistance in Community-Acquired Pneumonia Caused by Streptococcus Pneumoniae, Methicillin- Resistant S taphylococcus aureus, and Acinetobacter baumannii Ho CHEST 2009; 136:1119 The 2007 Infectious Diseases Society of America/American Thoracic Society guidelines recommended the addition of vancomycin or linezolid for empirical treatment of CAP if CA-MRSA is a consideration
  147. 147. <ul><li>In general, CA-MRSA is usually susceptible in vitro to vancomycin, linezolid, trimethoprim-sulfamethoxazole, rifampin, and tigecycline. CA-MRSA is sometimes susceptible to clindamycin, but the D-test has to be done to determine the presence of in vitro inducible resistance. </li></ul><ul><li>From 2003 to 2004, all of the CA-MRSA isolates were uniformly resistant to macrolides, and one-half of them were not susceptible to treatment with fluoroquinolones. </li></ul>Treatment of CA-MRSA Pneumonia Antibiotic Resistance in Community-Acquired Pneumonia Caused by Streptococcus Pneumoniae, Methicillin- Resistant S taphylococcus aureus, and Acinetobacter baumannii Ho CHEST 2009; 136:1119 Linezolid (10 mg/Kg 8-12 h in chidren) may be a better choice due to its good pharmacokinetic profile in the lung
  148. 148. <ul><li>In the 2009 British Thoracic Society guidelines for CAP, combination therapy with linezolid, clindamycin, and rifampicin is recommended when necrotizing pneumonia caused by PVL-positive S aureus is strongly suspected. </li></ul><ul><li>For patients with influenza and CA-MRSA coinfection, combined therapy with an antibiotic and an antiviral agent should be considered. </li></ul><ul><li>In a mouse model of postinfluenza pneumococcal pneumonia, it was found that ampicillin alone did not improve mortality. When the mice were treated with both oseltamivir and ampicillin, all deaths were prevented. </li></ul>Antibiotic Resistance in Community-Acquired Pneumonia Caused by Streptococcus Pneumoniae, Methicillin- Resistant S taphylococcus aureus, and Acinetobacter baumannii Ho CHEST 2009; 136:1119 Treatment of CA-MRSA Pneumonia
  149. 149. <ul><li>A baumannii is an aerobic Gram-negative coccobacillus that is ubiquitous in soil and fresh water, and it is a well-known and common cause of hospital-acquired A baumannii pneumonia (HAP-AB). </li></ul><ul><li>In contrast, CAP-AB has been reported sporadically in Asian-Pacific countries, especially during the warmer and more humid seasons. </li></ul><ul><li>CAP-AB tends to affect older people. </li></ul><ul><li>Reported risk factors are cigarette smoking and COPD, alcoholism, diabetes mellitus, organ failures, and malignancies. </li></ul>Antibiotic Resistance in Community-Acquired Pneumonia Caused by Streptococcus Pneumoniae, Methicillin- Resistant S taphylococcus aureus, and Acinetobacter baumannii Ho CHEST 2009; 136:1119 Community-Acquired A BAUMANNII Pneumonia
  150. 150. <ul><li>A baumannii strains isolated in patients with CAP-AB are generally resistant to treatment with ampicillin, cefotaxime, chloramphenicol, aztreonam, and cefoperazone. </li></ul><ul><li>A baumannii strains were sensitive to aminoglycosides , antipseudomonal penicillins, imipenem, fluoroquinolones and ceftazidime. </li></ul>Antibiotic Resistance in Community-Acquired Pneumonia Caused by Streptococcus Pneumoniae, Methicillin- Resistant S taphylococcus aureus, and Acinetobacter baumannii Ho CHEST 2009; 136:1119 Community-Acquired A BAUMANNII Pneumonia
  151. 151. <ul><ul><li>MRSA as a cause of community-acquired pneumonia </li></ul></ul><ul><li>Nakou ERJ 2009:34:1013 </li></ul>S. aureus has led to a multidrug-resistant pathogen, meticillin-resistant S. aureus (MRSA) after the introduction of methicillin into clinical practice in the 1960s. MRSA is resistant to β-lactam antibiotics, including penicillin and cephalosporins. Resistance is mediated by penicillin binding protein 2a, a penicillin binding protein encoded by the mecA gene that permits growth in the presence of methicillin.
  152. 152. <ul><ul><li>MRSA as a cause of community-acquired pneumonia </li></ul></ul><ul><li>Nakou ERJ 2009:34:1013 </li></ul><ul><li>MRSA was only a nosocomial pathogen. </li></ul><ul><li>In the mid 1990s, MRSA began to be detected in the community, i.e. community-acquired MRSA (CA-MRSA). It is the leading cause of identifiable skin and soft tissue infections seen in USA emergency rooms. </li></ul><ul><li>CA-MRSA may be associated with the presence of Panton Valentine leukocidin (PVL), a staphylococcal membrane toxin that targets leucocytes. PVL isolates have been linked to severe infections and necrotising pneumonia. </li></ul>
  153. 153. <ul><ul><li>MRSA as a cause of community-acquired pneumonia </li></ul></ul><ul><li>Nakou ERJ 2009:34:1013 </li></ul><ul><li>Compared with nosocomial MRSA, CA-MRSA isolates are commonly sensitive to antibiotics such as clindamycin, fluoroquinolones, trimethoprim–sulfamethoxazole, tetracyclines and rifampicin. </li></ul><ul><li>There is evidence of increasing prevalence of asymptomatic colonisation among children and adults in the community, which is typically resistant to β-lactam and macrolide antimicrobial agents and contains genes for PVL toxin. </li></ul>
  154. 154. <ul><ul><li>MRSA as a cause of community-acquired pneumonia </li></ul></ul><ul><li>Nakou ERJ 2009:34:1013 </li></ul><ul><li>Compared with nosocomial MRSA, CA-MRSA isolates are commonly sensitive to antibiotics such as clindamycin, fluoroquinolones, trimethoprim–sulfamethoxazole, tetracyclines and rifampicin. </li></ul><ul><li>There is evidence of increasing prevalence of asymptomatic colonisation among children and adults in the community, which is typically resistant to β-lactam and macrolide antimicrobial agents and contains genes for PVL toxin. </li></ul>Guidelines recommend vancomycin or linezolid.
  155. 155. <ul><ul><li>MRSA as a cause of community-acquired pneumonia </li></ul></ul><ul><li>Nakou ERJ 2009:34:1013 </li></ul><ul><li>Post-influenza staphylococcal pneumonia has been reported during influenza pandemics. </li></ul><ul><li>There is evidence of mechanisms indicating influenza interaction with S. aureus : an influenza-induced increase in S. aureus -specific adhesion throughout the respiratory tract and S. aureus -specific proteases, which may increase influenza viral replication. </li></ul><ul><li>MRSA should remain in the differential diagnosis of severe CAP occurring during the influenza season, especially in those with cavitary infiltrates and in those with a history of MRSA infection. </li></ul>
  156. 156. <ul><ul><li>What is MRSA? </li></ul></ul><ul><ul><li>Pantosti ERJ 2009:34:1190 </li></ul></ul><ul><li>Typically, CA-MRSA strains cause skin and soft tissue infections, including furuncles, abscesses, impetigo and cellulitis. </li></ul><ul><li>Infections are often recurrent and outbreaks have been reported. Rarely, CA-MRSA are associated with severe infections with high mortality, such as sepsis and Waterhouse-Friderichsen syndrome, necrotising fasciitis and necrotising pneumonia. </li></ul><ul><li>Necrotising pneumonia occurs in young patients, is often preceded by influenza virus infection or an influenza-like illness, is characterised by multiple cavitating lung infiltrates and mortality can exceed 50%. </li></ul>
  157. 157. <ul><ul><li>What is MRSA? </li></ul></ul><ul><ul><li>Pantosti ERJ 2009:34:1190 </li></ul></ul>The proportion of methicillin-resistant Staphylococcus aureus (MRSA) isolates from bloodstream infections in Europe in 2007.
  158. 158. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 <ul><li>Staphylococci are Gram-positive spherical bacteria that occur in microscopic clusters resembling grapes. </li></ul><ul><li>Staphylococcus aureus mainly colonises the nasal passages, but it may be found regularly in most other anatomical sites. </li></ul><ul><li>Carrier rates in adults vary from 20–50% with people being persistent carriers, intermittent carriers or noncarriers. </li></ul><ul><li>A large study found that 24% of people persistently carry S. aureus and 57% are intermittent carriers whilst 20% were never colonised. </li></ul>
  159. 159. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 Some of the virulence determinants of Staphylococcus aureus . TSST: toxic shock syndrome toxin.
  160. 160. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 <ul><li>S. aureus virulence factors include the following. </li></ul><ul><li>Surface proteins, for example protein A, that promote adherence and hence colonisation of host tissues. Different S. aureus strains may have different groups of these proteins predisposing them to different kinds of infections. </li></ul><ul><li>Invasions that promote bacterial spread in tissues (leukocidin, kinases and hyaluronidase). </li></ul><ul><li>Membrane damaging toxins that lyse eukaryotic cell membranes (haemolysins, leukotoxin and leukocidin). </li></ul><ul><li>Exotoxins that damage host tissues or otherwise provoke symptoms of disease (SAE-G, TSST-1, exfoliatin toxin and Panton–Valentine leukocidin (PVL)). </li></ul><ul><li>Inherent and acquired resistance to antimicrobial therapeutic agents. </li></ul>
  161. 161. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 Initially, MRSA was exclusively associated with acquisition from hospitals and other healthcare settings. However, in the late 1990s true CA-MRSA was identified as the cause of severe and fatal infections occurring in clusters of previously healthy children in North America, who had no identifiable associations with healthcare settings. Cases of CA-MRSA causing skin and soft tissue infections and necrotising pneumonia have since been widely reported in otherwise healthy individuals.
  162. 162. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 <ul><li>Hospital-acquired pneumonia (HAP) or nosocomial pneumonia is usually defined as pneumonia developing ≥ 48 h after admission to hospital that was not incubating at the time of admission. </li></ul><ul><li>Ventilator-associated pneumonia (VAP) is usually defined as pneumonia developing ≥ 48 h after implementation of endotracheal intubation and/or mechanical ventilation and which was not present prior to intubation. </li></ul><ul><li>VAP can be divided into early and late onset. Early-onset disease occurs within 4–5 days of admission and tends to be caused by antibiotic-susceptible community-type pathogens, whereas late-onset disease tends to be caused by antibiotic-resistant pathogens. </li></ul>
  163. 163. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 <ul><li>Hospital-acquired pneumonia (HAP) or nosocomial pneumonia is usually defined as pneumonia developing ≥ 48 h after admission to hospital that was not incubating at the time of admission. </li></ul><ul><li>Ventilator-associated pneumonia (VAP) is usually defined as pneumonia developing ≥ 48 h after implementation of endotracheal intubation and/or mechanical ventilation and which was not present prior to intubation. </li></ul><ul><li>VAP can be divided into early and late onset. Early-onset disease occurs within 4–5 days of admission and tends to be caused by antibiotic-susceptible community-type pathogens, whereas late-onset disease tends to be caused by antibiotic-resistant pathogens. </li></ul>However, some studies have found an increasing frequency of early-onset HAP caused by pathogens more commonly associated with nosocomial disease.
  164. 164. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 Healthcare-associated pneumonia HCAP, has been defined as pneumonia occurring in any patient who had: been admitted to an acute care hospital for ≥2 days within 90 days of the infection; been a resident in a nursing home or long-term care facility (LTCF); attended a hospital or haemodialysis clinic; or received recent intravenous antibiotic therapy, chemotherapy or wound care within the 30 days prior to the current infection.
  165. 165. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 In the European setting, S. aureus remains an unusual primary cause of community-acquired pneumonia (CAP), although it is an important cause of pneumonia and death following influenza.
  166. 166. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 HAP and VAP Until recently S. aureus accounted for ≈ 1–5% of CAP cases and ≈10–15% of HAP cases, but over the past 10–20 yrs there has been important changes in the epidemiology of Staphylococcal pneumonia . First, there has been a dramatic increase in the proportion of S. aureus infections due to MRSA, which is now responsible for >50% of all S. aureus infections in some intensive care units (ICUs).
  167. 167. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 HAP and VAP HAP requires the entry of microbial pathogens into the lower respiratory tract followed by colonisation which, if the body's defences are overwhelmed, leads to overt infection. Factors such as the severity of the patient's underlying disease, prior surgery, exposure to antibiotics, other medications, and exposure to invasive respiratory devices and equipment are important in the pathogenesis of HAP and VAP.
  168. 168. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 HAP and VAP HAP requires the entry of microbial pathogens into the lower respiratory tract followed by colonisation which, if the body's defences are overwhelmed, leads to overt infection. Factors such as the severity of the patient's underlying disease, prior surgery, exposure to antibiotics, other medications, and exposure to invasive respiratory devices and equipment are important in the pathogenesis of HAP and VAP. Early-onset disease, defined as within 4 days of hospitalisation, has a better prognosis and is more likely to be caused by antibiotic-sensitive bacteria.
  169. 169. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 HAP and VAP A prospective study comparing VAP outcome by causative pathogen demonstrated that, in patients who received appropriate initial antimicrobial therapy, cases due to MRSA still had a significantly slower clinical resolution than those due to other pathogens. Resolution of fever and hypoxia within 72 h occurred in only 30% of MRSA VAP cases, compared to 93.3% of methicilin-sensitive S. aureus (MSSA) VAP cases, 100% due to H. influenzae and 73% due to Pseudomonas aeruginosa . Vidaur L. Eur Respir Rev 2007;16:31–32
  170. 170. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 A new form of CAP There has been an emergence of CA-MRSA CAP being reported on both sides of the Atlantic. Although CA-MRSA is primarily a cause of skin and soft tissue infections, it can also cause severe necrotising pneumonia. Characteristics of CA-MRSA CAP often frequently occur in young previously healthy adults, up to 75% of cases, with a preceding flu-like illness. Sufferers rapidly develop severe respiratory symptoms, often including haemoptysis, hypotension and a high fever. Characteristically, leukopenia occurs and C-reactive protein is elevated (>350 g·L –1 ). CXR findings of multilobar cavitating alveolar infiltration are also consistent with CA-MRSA.
  171. 171. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 when to suspect CA-MRSA in community-acquired pneumonia When to suspect CA-MRSA Influenza-like prodrome Severe respiratory symptoms with a rapidly progressive pneumonia evolving to acute respiratory distress syndrome Fever >39°C Haemoptysis Hypotension Leukopenia Chest radiograph showing multilobar infiltrates which may have cavitated Known to be colonised with CA-MRSA or recent travel to an endemic area, such as North America, and recent contact with CA-MRSA Belong to a group associated with increased rates of colonisation of CA-MRSA Previous history or family history of recurrent furuncles or skin abscesses (two or more in past 6 months) CA-MRSA: community-acquired methicillin-resistant Staphylococcus aureus . Nathwani J Antimicrob Chem 2008;61:976
  172. 172. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470
  173. 173. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 INVESTIGATIONS FOR STAPHYLOCOCCAL PNEUMONIA <ul><li>Obtaining isolates of the organism </li></ul><ul><li>Endotracheal cultures should not be used to diagnose VAP as bronchoalveolar lavage specimens are preferred. </li></ul><ul><li>For HAP nonbronchoscopy-directed (blind) bronchoalveolar lavage should be used. </li></ul><ul><li>Blood cultures are more likely to be positive in secondary pneumonia where the primary source is elsewhere, such as infective endocarditis or discitis, rather than in primary pneumonia (90% versus 20%). </li></ul>
  174. 174. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 INVESTIGATIONS FOR STAPHYLOCOCCAL PNEUMONIA <ul><li>The antibiogram: antibiotic sensitivities </li></ul><ul><li>After isolating S. aureus , sensitivity testing for various antibiotics will determine whether it is MRSA or not, and which antibiotics may be clinically effective. </li></ul><ul><li>The antibiogram of CA-MRSA is commonly only resistant to the β-lactams and susceptible to most other antibiotic classes. </li></ul>
  175. 175. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 INVESTIGATIONS FOR STAPHYLOCOCCAL PNEUMONIA Molecular techniques Novel laboratory techniques, including microarrays to detect PVL and possibly other staphylococcal toxins or superantigens, may aid in the diagnosis of CA-MRSA pneumonia. These microarrays can reveal if the isolates are harbouring the genes for several toxins including PVL and leukocidin, which have been linked with pulmonary disease and have been associated with CA-MRSA isolates. Also under investigation and development are molecular-based rapid tests to detect PVL, mec A and SCC mec type IV.
  176. 176. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 INVESTIGATIONS FOR STAPHYLOCOCCAL PNEUMONIA <ul><li>Radiological investigations </li></ul><ul><li>No radiological features are highly specific for Staphylococcal pneumonia. Early in the disease progression of CAP with S. aureus there may be minimal infiltrates but they rapidly progress, even within hours. </li></ul><ul><li>Infiltrates are more likely to cavitate, which may be seen on serial CXR and best confirmed by a computed tomography scan. Pleural effusions, pneumatoceles and pneumothoraces are also common findings. </li></ul>
  177. 177. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 INVESTIGATIONS FOR STAPHYLOCOCCAL PNEUMONIA <ul><li>Radiological investigations </li></ul><ul><li>No radiological features are highly specific for Staphylococcal pneumonia. Early in the disease progression of CAP with S. aureus there may be minimal infiltrates but they rapidly progress, even within hours. </li></ul><ul><li>Infiltrates are more likely to cavitate, which may be seen on serial CXR and best confirmed by a computed tomography scan. Pleural effusions, pneumatoceles and pneumothoraces are also common findings. </li></ul>Clinically however, there may be a suspicion of MRSA as the causative organism in VAP as patients tend to have more severe disease and respond more slowly to appropriate antimicrobial therapy.
  178. 178. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 Necrotising pneumonia on A ) a chest radiograph and B ) a computed tomography (CT) scan obtained on day 3. The CT scan shows multiple bilateral nodular and cavity lesions.
  179. 179. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470 <ul><li>The frequency of pneumonia caused by HA-MRSA and CA-MRSA is increasing. </li></ul><ul><li>HA-MRSA traditionally occurs in the hospital setting. </li></ul><ul><li>A new form of MRSA, more virulent and frequently more toxin producing (including PVL toxin), is emerging from the community. It is primarily affecting young healthy individuals and has a high mortality rate. </li></ul><ul><li>Vancomycin has been disappointing in treating MRSA pneumonia and although linezolid may be a better choice. </li></ul><ul><li>Combination therapy with clindamycin and immunoglobulin may be helpful in cases of CA-MRSA where there is PVL production causing haemorrhagic and necrotising pneumonia. </li></ul>CONCLUSIONS
  180. 180. Effect of Linezolid Compared With Glycopeptides (Vancomycin, Teicoplanin) in Methicillin-Resistant Staphylococcus aureus Severe Pneumonia in Piglets Luna Chest 2009;135:1564 Infected with MRSA Severe pneumonia <ul><li>Lung pathology score was lower in those receiving LZD vs those receiving glycopeptides (Vancomycin, Teicoplanin) (p=0.049) </li></ul><ul><li>Survival at 72 h was higher in the LZD. </li></ul>
  181. 181. The survival time up to 72 hours analyzed for the different groups Pathology score according to the different AMT received by the piglets. AMT= antimicrobial therapy MV= mechanical ventilation Effect of Linezolid Compared With Glycopeptides (Vancomycin, Teicoplanin) in Methicillin-Resistant Staphylococcus aureus Severe Pneumonia in Piglets Luna Chest 2009;135:1564
  182. 182. Macrolide resistance in Streptococcus pyogenes : A marker of an overuse of macrolides Matti Korppi, Ped Pulmonol 2009;44:1246 <ul><li>There is no need to treat pharyngitis by macrolides, since nearly all streptococcal strains are sensitive to penicillin and cephalosporins. </li></ul><ul><li>Thus, macrolide resistance in S. pyogenes is not a therapeutic problem, not even in penicillin-allergic patients who can be treated, for example, by cephalosporins. </li></ul><ul><li>Merely, macrolide resistance in S. pyogenes is a marker of an overuse of macrolides in the population , and the true problem is the development of macrolid resistance in S. pneumoniae . </li></ul>
  183. 183. <ul><li>Thus, macrolides cannot be used any more as an only drug in the treatment of community-acquired pneumonia (CAP) in children , even though Mycoplasma pneumoniae or Chlamydia pneumoniae is suspected . </li></ul><ul><li>M.pneumoniae and C. pneumoniae together cause over half of the CAP cases in over 5 years old and even more in over 10 years old children. However, S. pneumoniae should be covered also in these cases, since a third of atypical bacterial CAP cases are mixed infections with pneumococcus . Korppi M., Respirology 2004;9:109. </li></ul>Macrolide resistance in Streptococcus pyogenes : A marker of an overuse of macrolides Matti Korppi, Ped Pulmonol 2009;44:1246
  184. 184. A Randomized Trial of Dental Brushing for Preventing Ventilator-Associated Pneumonia Pobo Chest 2009;136:433 <ul><li>adult patients intubated for > 48 h </li></ul><ul><li>oral care every 8 h with 0.12% chlorhexidine digluconate (standard group) or standard oral care plus electric toothbrushing (toothbrush group) </li></ul><ul><li>147 patients (74 toothbrush group) </li></ul>Kaplan-Meier curve comparing VAP incidence in toothbrush and standard groups.
  185. 185. A Randomized Trial of Dental Brushing for Preventing Ventilator-Associated Pneumonia Pobo Chest 2009;136:433 <ul><li>adult patients intubated for > 48 h </li></ul><ul><li>oral care every 8 h with 0.12% chlorhexidine digluconate (standard group) or standard oral care plus electric toothbrushing (toothbrush group) </li></ul><ul><li>147 patients (74 toothbrush group) </li></ul>Kaplan-Meier curve comparing VAP incidence in toothbrush and standard groups. The toothbrush group and standard group had similar rates of suspected VAP (20.3% vs 24.7%; p= 0.55).
  186. 186. A Randomized Trial of Dental Brushing for Preventing Ventilator-Associated Pneumonia Pobo Chest 2009;136:433 <ul><li>adult patients intubated for > 48 h </li></ul><ul><li>oral care every 8 h with 0.12% chlorhexidine digluconate (standard group) or standard oral care plus electric toothbrushing (toothbrush group) </li></ul><ul><li>147 patients (74 toothbrush group) </li></ul>Kaplan-Meier curve comparing VAP incidence in toothbrush and standard groups. The addition of electric toothbrushing to standard oral care with 0.12% chlorhexidine digluconate is not effective for the prevention of VAP
  187. 187. Nonresolving pneumonia and rash in an adult: pulmonary involvements in Kawasaki's disease Ugi ERJ 2010;35:452 <ul><li>Slowly resolving or nonresolving pneumonia is a challenge for physicians. </li></ul><ul><li>The most common clinical error when approaching these patients is to subsequently treat the patient with different antibiotics over an extended period of time, without questioning the cause of treatment failure. </li></ul><ul><li>Mostly, slowly resolving pneumonias are due to host defence or infectious causes. </li></ul><ul><li>Nonresolving pneumonias are usually of noninfectious origin and, in the majority of cases, require invasive diagnostic techniques to be confirmed. </li></ul>
  188. 188. Nonresolving pneumonia and rash in an adult: pulmonary involvements in Kawasaki's disease Ugi ERJ 2010;35:452 <ul><li>A 19-yr-old male developed dyspnoea, dry cough and bilateral reticulo-nodular infiltrates on chest radiograp

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