1. Special Lecture รพ. ชัยภูมิ Rattapon Uppala, MD Division of Pulmonology and critical care Faculty of Medicine Khon Kaen University Lower Respiratory tract Infection

2. Lung protective mechanism

3. Intrinsic lung defenses Aerodynamic filtering Humidification Airway reflexes –Sneezing –Bronchoconstriction –Cough reflex Mucus and airway surface liquid –Respiratory mucus –Mucocilliary clearance

4. Aerodymanic Filtering Very large particles: Nasal hair Particles < 0.2 μm may not sediment and are exhaled Particles 2 - 10 μm: walls of the branching airways beyond the nose, sedimentation Particles 0.2 - 2 μm: Surface of the alveoli Particles > 10 μm: Surfaces of turbinate & septum Stark JM, Colasurdo GN. In Kendig's Disorders of the Respiratory Tract in Children;2006:205-23.

5. Abnormalities of Cough Mechanism Abnormalities of cough mechanism Conditions Decreased cough center sensitivityUnconsciousness, Drugs e.g. opiates Decreased cough receptor sensitivity Recurrent aspiration,GER Abnormality of efferent nervesPoliomyelitis, Infantile botulism Abnormality of muscleNeuromuscular diseases e.g. SMA, muscular dystrophy Ineffective laryngeal closureVocal cord paralysis Presence of a tracheostomy tube

7. Sinus Moist air space Four pairs of sinuses : ethmoid, maxillary, frontal, sphenoid –Ethmoid and maxillary sinuses form, present at birth –Only ethmoid sinuses are pneumatized at birth –Maxillary sinuses are pneumatized by 4 years of age –Sphenoid sinuses are pneumatized by 5 years of age –Frontal sinuses appear at age 7 - 8 years, completely developed in late adolescence Nelson Textbook of Pediatrics, 19 th edition

9. Pathogenesis Ostia obstruction  hypoxic environment within sinus Retention of secretion  inflammation and bacterial infection Secretion stagnate  obstruction increases  cilia and epithelial damage Nelson Textbook of Pediatrics, 19 th edition

10. Criteria for the Diagnosis of Sinusitis Presence of at least 2 Major or 1Major and ≥ 2 Minor IDSA Guideline for ABRS. Clin Infect Dis. 2012 ; 54(8): e72 – e112

11. Antimicrobial Regimens for ABRs in Children Not azithromycin, clarithromycin, co-trimoxazole for empiric Rx for ABRS Variable susceptibilities to oral 2 nd, 3 rd cephalosporins IDSA Guideline for ABRS. Clin Infect Dis. 2012 ; 54(8): e72 – e112

12. Treatment Amoxicillin (45 mg/kg/day) for uncomplicated case Penicillin-allergic : TMP-SMX, cefuroxime axetil, cefpodoxime, clarithromycin, or azithromycin Recommend for 7 days after resolution of symptoms High-dose amoxicillin-clavulanate (80-90 mg/kg/day of amoxicillin) PRSP group –Antibiotic treatment in the preceding 1-3 mo –Daycare attendance –Age <2 yr –Presence of resistant bacterial species –Failed to respond to initial therapy with amoxicillin within 72 hr intranasal corticosteroids for allergic rhinitis co-morbidity Nasal irrigation Nelson Textbook of Pediatrics, 19 th edition

13. Croup Parainfluenza virus 1, 2, 3 (75%), RSV, Adenovirus, Herpesviruses (severe), Measle, Mycloplasma Preschool age, Peak 18 - 24 months

14. Swelling and inflammation in the subglottic area Secretions in the airway lumen Leukocytes infiltrate the subepithelium  vascular congestion and airway wall edema Spasmogenic mediators Pathogenesis

15. Diagnosis Croup is clinical diagnosis : dose not required a radiograph of neck, AP neck : steeple sign Clinical012 CoughNoneHoarse cryBarking cough StridorNoneInspiration Inspiration and expiration Breath soundNormal Harsh with rhonchi delay RetractionNone Nasal flaring, suprasternal Subcostal, intercostal CyanosisNoneIn room airIn 40% oxygen

16. Assess croup score 7 - รักษาแบบผู้ป่วยนอก - พ่น adrenaline (1:1000) 0.05-0.5 มก./ กก./ ครั้ง -Intubation - ให้การรักษาแบบประคับประคอง ( อายุ <4 ปี ขนาดสูงสุด 2.5 มล.) -Dexamethasone - ติดตามการรักษาภายใน 24 ขม. ( อายุ >4 ปี ขนาดสูงสุด 5 มล. ) - No other underlying Dz - Dexamethasone 0.6 มก./ กก./dose IV./IM.OD max dose10mg/dose ดีขึ้นไม่ดีขึ้น ให้ adrenaline ซ้ำได้ทุก 2-6 ชม. ดูอาการต่ออีก > 24 ชม. ดีขึ้น ไม่ ดีขึ้น ดูอาการต่ออย่างน้อย 24 ชม. ให้ adrenaline ซ้ำ Intubation ได้ทุก 2-6 ชม.

17. Staphylococcus aureus : most common, HiB, streptococcus, pneumococcus, M. catarrhalis, Gram neg: Pseudomonas aeruginosa Primary bacterial infection or secondary to viral croup Deteriorate rapidly, high fever, toxic appearance, respiratory distress and airway obstruction Not respond to corticosteroid or nebulized epinephrine Bacterial tracheitis

18. Subglottic edema with ulceration, erythema Pseudomembranous formation on tracheal surface Thick, mucopurulent secretion and sloughed mucosa frequently obstruct the lumen Lateral neck X-ray –hazy tracheal air column –Irregularities of the trachea wall Pathophysiology

19. Diagnostic endoscopy under GA; enable removal of secretion and sloughed tissue Many patient required ET intubation, usually 3-7 days Frequent tracheal suction IV broad spectrum antibiotics 10-14 days Treatment

20. Bronchitis Nonspecific inflammation of bronchus Usually viral in origin, follows upper respiratory tract infection Cough  prominent feature, Vomiting (swallowed sputum), Chest pain, Low grade fever (or absent) Common in younger children(< 6 yrs) and males Nelson Textbook of Pediatrics, 19 th edition

21. Management Supportive treatment Adequate hydration, rest, and proper humidification of the ambient air Frequent shifts in position can facilitate pulmonary drainage in infants Avoided cigarette smoke Cough suppressant is contraindicated Wheezing  trial of a β agonist Antibiotic if indicated Steroids, either inhaled or systemic: poorly defined Nelson Textbook of Pediatrics, 19 th edition

22. Bronchiolitis Younger than 2 years of age, 1 st episode of wheezing RSV(50-80%), HMPV (19%), other viruses Clinincal viral infection, followed by onset of tachypnea, chest retraction, wheezing or prolong expiratory phase, apnea Peak symptom around day 3-4 of illness Diagnose by history and physical examination Virology: viral culture, IFA, EIA, PCR, NP aspiration Kendig& Chernick’s disorders of the respiratory tract inchildren. 8 th edition 2012

23. Pathogenesis RSV binds to TLR-4 on epithelium Cellular and ciliary damage, inflammatory effect Mucus secretion combining with desquamated epithelial cells  “Thick mucus plug”  Bronchiolar obstruction  air trap or collapse Mucous plugs are removed by macrophages Recovery after regeneration of the bronchiolar epithelium 3-4 days, cilia 15 days RSV: Viral shedding time 8 days Kendig& Chernick’s disorders of the respiratory tract inchildren. 8 th edition 2012

24. Severity assessment Poor feeding and respiratory distress Severity factors –Toxic or ill appearance –O 2 < 95% with room air –Age younger than 3 mo. –RR ≥ 70 breath per min –Atelectasis on chest radiography Kendig’s disorders of the respiratory tract inchildren. 7 th edition 2006

25. Treatment Supportive treatment –Humidified oxygen –Adequate hydration, Beware SIADH –Nasal suctioning Symptomatic treatment –Antipyretic drug + Tepid sponge –Trial nebulized adrenaline, salbutamol –Systemic corticosteroid, Leukotriene Modifiers –Hypertonic saline –Heliox inhalation therapy –CPAP or high flow oxygen Specific treatment –Ribavirin and anti RSV medication –RSV Immunoglobulins prophylaxis (RSV Ig and Palivizumab) Kendig’s disorders of the respiratory tract inchildren. 7 th edition 2006

26. Complication Early –Respiratory failure (esp. <6 mo, preterm) –AOM (50-60%) –Myocarditis –SIADH Late –Asthma / reactive airway disease  recurrent wheezing >50% and abnormal PFT –Bronchiolitis obliterans Most common : adenovirus, especially serotypes 1, 3, 7 and 21, RSV Kendig& Chernick’s disorders of the respiratory tract inchildren. 8 th edition 2012

27. CXR : hyperinflation and bilateral interstitial markings HRCT : mosaic perfusion, vascular attenuation Anti-inflammatory drug : Azithromycin Corticosteroids have not been shown to improve outcome Lung transplantation Kendig& Chernick’s disorders of the respiratory tract inchildren. 8 th edition 2012

28. Inflammation of lung tissue caused by infectious agent resulting in damage to lung tissue Thailand : 45-50% of LRTI children below 5 years of age, most common cause of death Pneumonia Kendig& Chernick’s disorders of the respiratory tract inchildren. 8 th edition 2012

29. 40% are caused by viral infections (WHO 2008)

30. Pathogenesis Viral pneumonia –Interstitial inflammation –Alveolar walls thicken, occluded with exudates, sloughed cells, and macrophages –Inflammation of the bronchioles, and air trapping Bacterial pneumonia –Organisms colonize the trachea  access to the lungs or direct seeding after bacteremia –Alveolar inflammation Kendig& Chernick’s disorders of the respiratory tract inchildren. 8 th edition 2012

31. Pediatrics in Review 2008;29;147 Tachypnea : useful sign for the diagnosis of childhood pneumonia

32. Gold standard : lung puncture specimen or performing a bronchoalveolar lavage Chest radiograph –Viral : hyperaeration, prominent lung markings (bronchiolar thickening) and focal atelectasis –Bacterial : alveolar infiltration, lobar consolidation, linear filtration, pleural effusion, pneumatocele Diagnosis Kendig& Chernick’s disorders of the respiratory tract inchildren. 8 th edition 2012

33. Pediatrics in Review 2008;29;147

34. Recommended Microbiological investigations Blood cultureFor all hospitalized, positive less than 10% Nasopharyngeal aspirate (NPA) for viral antigen detection For all under 18 months of age, highly specific and sensitive for RSV, influenza and adenovirus Nasopharyngeal aspirate viral culture if virus not detected by antigen detection, highly specific and sensitive SerologyAcute and convalescent serology for viruses, Mycoplasma and Chlamydia Pleural aspirate (if present)Microscopy, culture and bacterial antigen detection (pneumococcal) Bacterial antigen in urineNOT recommended due to poor specificity Nasopharyngeal aspirate (NPA) bacterial culture NOT recommended as not of diagnostic value Serum antigens (bacterial)NOT recommended as tests are less sensitive and specific Review of BTS guidelines for the management of community acquired pneumonia in children. Journal of Infection (2004) 48, 134–138

35. Age < 3 mo SpO2 at room air < 92% Respiratory distress : retraction, grunting difficult breath,apnea Sign of dehydration, poor feeding Drowsiness or sign of shock Suspected S.aureus pneumonia Underlying CHD, CLD, immune deficiency Not response in OPD treatment 48 hr and clinical progression Poor childcare attendance Criteria for admission ชมรมโรคระบบหายใจและเวชบำบัดวิกฤตในเด็กแห่งประเทศไทย 2556

36. Treatment Supportive & Symptomatic treatment -Oxygen therapy -Adequate hydration -Bronchodilator -Expectorant or mucolytic -Chest physical therapy -Antipyretic Specific treatment -Antiviral, Antibiotic Prevention -Vaccine -Infectious control : isolation, hand hygiene ชมรมโรคระบบหายใจและเวชบำบัดวิกฤตในเด็กแห่งประเทศไทย 2556

37. Kendig& Chernick’s disorders of the respiratory tract inchildren. 8 th edition 2012

38. Parapneumonic effusion Pneumatocele, pneumothorax Lung abscess Septicemia and metastatic infection Hemolytic uremic syndrome Extrapulmonary in M.pneumoniae : rash, SJS, hemolytic anemia, polyarthritis, hepatitis, pancreatitis, myocarditis, encephalitis, aseptic meningitis and transverse myelitis Long term : chronic lung disease, bronchiectasis Complication ชมรมโรคระบบหายใจและเวชบำบัดวิกฤตในเด็กแห่งประเทศไทย 2556

39. Pulmonary abscess Thick walled purulent material, result of infection destructing lung parenchyma, cavitating and central necrosis –Primary lung abscess –Secondary lung abscess Predispose conditions : aspiration (most common in children), pneumonia, cystic fibrosis, GER, TE fistula, immunodeficiency, postoperative complication T&A, seizure, neurologic disease Nelson Textbook of Pediatrics, 19 th edition

40. Aspiration Effected sites –Recumbent position : RUL, LUL, apical segment of RLL –Upright position : posterior segment of RUL Organism : Mixed organism –Anaerobes (Bacteroides, Fusobacterium, Peptostreptococcus) –Aerobes (Strep, Staph, E.coli, Klebsiella, Pseudomonas) –Fungus particularly immunocompromised patients Nelson Textbook of Pediatrics, 19 th edition

41. Diagnosis CXR abcess = parenchymal inflamation with cavity containing air-fluid level CXR pneumatoceles = thin and smooth walled, localized air collection with or without air-fluid level Sputum C/S : mixed organism, not reliable CT-guided percutaneous or transtracheal aspiration or BAL Nelson Textbook of Pediatrics, 19 th edition

43. Treatment ATB : IV 2-3 wks, then oral for total 4-6 wks Initial broad spectrum ATB with aerobic (S.aureus) and anaerobic coverage : Clindamycin or BL/BI or PGS + Metronidazole Severely ill or fails medication after 7-10 days of appropiate ATB : minimal invasive percutaneous aspiration –rare for thoracotomy with surgical drainage or lobectomy and/or decortication Excellent prognosis –Fever can persist for 3 wk –CXR resolve in 1-3 mo, can persist for year Nelson Textbook of Pediatrics, 19 th edition

44. Lower Respiratory Tract Infections in Children Summary

45. Definition & Etiology  There is no hard and fast definition of lower respiratory tract infection (LRTI), that is universally adopted.  Essentially, it is inflammation of the airways/pulmonary tissue, due to viral or bacterial infection, below the level of the larynx.

46. Viral causes  Influenza A  Respiratory Syncytial Virus (RSV)  Human Metapneumovirus 4  Varicella-Zoster Virus (VZV - Chickenpox)  Adenovirus  Para-influenza virus

47. Bacterial Agents  Streptococcus pneumoniae  Hemophilus Influenzae  Staphylococcus aureus  M  Klebsiella pneumoniae  Enterobacteria e.g. E. coli  Anaerobes

48. Atypical Agents  Mycoplasma pneumoniae  Legionella pneumophila  Chlamydia sp.  Coxiella burnetii

49. Clinical Picture Presentation Acute febrile illness, possibly preceded by typical viral URTI. Symptoms : 1.Cough 2.Breathlessness ( preventing feeding) 3.Irritability 4.Sleeplessness 5.Chest or abdominal pain in older patients  Audible wheezing is rare in LRTI, but can occur

50. Physical Signs 1.Capillary blood oxygen saturation <95% 2.Intercostal and supra-sternal recession 3.Flushing 4.Tachypnea 5.High fever over 38.5 c 6.Nasal flaring in children under 1 yr of age 7.Dullness to percussion over zones of pneumonia consolidation. 8.Cyanosis in severe cases.

51. Investigations Chest radiography if fever and tachypnea, oxygen saturation to monitor condition. In hospital consider capillary or arterial blood gases. Culture of sputum or nasopharyngeal discharge/aspirate may be used in hospital but has little to add in primary care. Blood cultures if evidence of septicemia. Blood urea and electrolytes

52. Management Admission for children under 5 years with fever and breathlessness is mandatory. Older children can be managed with close observation at home if not distressed Physiotherapy has no place in treatment of uncomplicated pneumonia in children without pre-existing respiratory disease.

53. Essential consideration Oxygen IV fluids if unable to feed Respiratory support in severe cases Cough medicines are not indicated and may be used if cough interferes with feeding or sleep. Honey with lemon may be helpful. Antihistamines are dangerous in young children & should be avoided.

54. Medications Antipyretics (avoid aspirin in young children due to danger of Reye's syndrome). Antibiotic treatment for bacterial pneumonias. Pneumonia or LRTI following URTI is likely to be viral and will not respond to antibiotic therapy. However, it is difficult to distinguish between viral and bacterial infection and young children can deteriorate rapidly. so consider antibiotic therapy depending on presentation and the clinical judgment of the concerned child.

55. Antibiotics Streptococcal pneumonia is treated with oral penicillin V, or synthetic penicillin such as amoxicillin as first line drugs. Recent research indicates that children with non-severe pneumonia on amoxicillin for 3 days do as well as those who receive it for 5 days If a child is genuinely allergic to penicillin, consider using a macrolide or quinolone. Cephalosporin often cross-react with penicillin.

56. Antibiotics For Hemophilus influenzae cephalosporins or Amoxicillin/Calvulenic acid combination are useful. For Staph pneumonia cloxacillin is used and in severe cases parenteral vancomycin is required. Injectable antibiotics are indicated in severe cases

57. Complications  Bacterial invasion of the lung tissue can cause: –pneumonic consolidation –septicemia –empyema –lung abscess (esp. S. Aureus) –pleural effusion –Mycoplasma P. can cause hemolysis –Rarely, respiratory failure, hypoxia and death.

58. Prevention It is achieved with pneumococcal vaccine and influenza vaccine Stop indoor smoking. Smoking at home or school is a major risk factor. Zinc supplementation reduces the incidence of pneumonia by over 40% in malnourished children.

59. Thank you