2. Bronchiolitis

3. Bronchiolitis Risk factors

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. 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. 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.

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

21. Bronchiolitis Assesment

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.

31. BronchiolitisTreatment

32. Bronchiolitis: Recent Evidence on Diagnosis and Management Zorc Pediatrics 2010;125:342 Summary of Recent Evidence for Therapies Used for Bronchiolitis

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. 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. 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. 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

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.

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. 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. % 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. 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.

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. “… 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

52. HOME OXYGEN FOR CHILDREN WITH ACUTE BRONCHIOLITIS Tie Arch Dis Child 2009;94:641

54. Bronchiolitis Long-term consequences

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. 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.

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. Cough in the Pediatric Population Goldsobel J Pediatr 2010;156:352

77. Cough in the Pediatric Population Goldsobel J Pediatr 2010;156:352 Algorithm for evaluating chronic cough in children

78. Cough in the Pediatric Population Goldsobel J Pediatr 2010;156:352 Algorithm for evaluating specific chronic cough in children

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

87. Pnumonia

88. Pnumonia Risk factors

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. 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.

105. Pnumonia Etiology atypical bacteria

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. Pnumonia assesment

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

124. Pnumonia treatment

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.

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.

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. 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. 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. 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. 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. 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. 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. 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. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia Defres ERJ 2009:34:1470

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.

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.

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