Pneumonia: An Update

1. Pneumonia: An Update fischer.phil@mayo.edu GMHC, Louisville November 2014

2. Objectives • Describe how to appropriately diagnosis pneumonia in a febrile coughing child; be able to articulate the limitations of various diagnostic modalities • Implement appropriate evidence-based treatment for children with severe lower respiratory infections of both bacterial and viral etiology

3. A Child A 10 month old child presents with two days of fever and cough. What is needed to appropriately make a diagnosis? What treatment is most likely to help?

6. Pneumonia 1,200,000 deaths per year Many cases vaccine-preventable ~30% of children provided antibiotics World Health Organization, 2012

7. Pneumonia 1,200,000 deaths per year >> ACT ! 18% of under 5 deaths ~3200 deaths per day Vaccine-Preventable >> PREVENT !! Inadequate Care >> Dx & Rx !!! World Health Organization, 2012 www.who.int/mediacentre/factsheets/fs331/en J Trop Pediatr 60:91-92, 2014

9. A 10 month old is febrile and coughing. What equipment is most useful in establishing a diagnosis? • A blood count machine • An x-ray machine • A stethoscope • None of the above

11. Tachypneaas a means of diagnosing “pneumonia” 2 - 12 months > 50 breaths / minute 12 - 60 months > 40 breaths / minute IF tachypnea (or severe retractions), give antibiotic. IF very sick, hospitalize for parenteral therapy.

13. What Causes Fever and Tachypnea?

14. What Causes Fever and Tachypnea? Bacterial Pneumonia Malaria Viral Respiratory Infection Fever Plus: Metabolic Acidosis - diabetes - dehydration Anxiety

15. Diagnosis of Pneumonia(Identification of Need for Antibiotics)

16. Pediatr Infect Dis J 29:406, 2010

17. 1622 children < 5 yo with “possible pneumonia” emergency department, Boston 20% of tachypneic children >> x-ray pneumonia 12% non-tachypneic >> radiographic pneumonia So, RR is not discriminating, but RR is somewhat predictive Pediatr Infect Dis J 29:406, 2010

18. Boston emergency department, 2574 pts < 21yrs If O2 sat < 92%, 37% - radiographic pneumonia If also no wheeze, 51% pneumonia If also focal rales, 70% pneumonia Tachypnea and retractions NOT linked to dx Pediatrics 128:246, 2011

19. Boston again, emergency department, 2008 kids Tachypnea vs Radiographic Pneumonia Age Sens Spec Pos Pred Value 2-12 mo 25% 76% 11% 1-5 yrs 37% 72% 24% Pediatr Infect Dis J31:561, 2012

20. Diagnosis of Pneumonia(Maybe x-ray is not definitive?) < 6 mo old, admitted, lower respiratory infection 40 chest x-rays reviewed by pediatric radiologists Kappa FINDING Within Between “consolidation” .91 .79 “normal” .80 .66 “airway disease” .68 .48 Pediatr Infect Dis J 15:600-604, 1996

21. Diagnosis of Pneumonia(Identification of Need for Antibiotics) Maybe x-ray is not definitive? PLOS One 5:e11989, 2010

22. Pneumonia Dx – Better than X-Ray?

23. Ultrasound to Diagnose Pneumonia? New York emergency department, 20 children H1N1 epidemic, 2009 Intra-Observer Reliability to Differentiate Bacterial vs Viral vs Both vs Neither (K = 0.82) Critical Ultrasound Journal 4:16, 2012

24. Ultrasound to Diagnose Pneumonia? New York emergency department 200 children, 1-8 years of age, 18% “pneumonia” Ultrasound with x-ray as “gold standard” 86% sensitivity 89% specificity JAMA Pediatr 167:119, 2013

26. Ultrasound vs X-Ray 163 children in Taiwan, 2010-2012 Clinical diagnosis of “pneumonia” Chest x-ray + in 152 and ultrasound in 159 Ultrasound finding of air bronchograms most helpful Ultrasound a “complementary tool” Ho MC et al. Pediatrics and Neonatology 2014

27. Causes of Pneumonia Pediatr Infect Dis J 31:e78, 2012

28. Causes of Pneumonia Viral PCR RSV, Metapneumovirus, or Parainfluenza positive Likely Causative Coronavirus and Enterovirus positive Cases ~ Controls Pediatrics 133:e538, 2014 Pediatr Infect Dis J 31:e78, 2012

29. Antibiotics for Pneumonia < 2 months: Hospitalize amp/gent 2+ mo, outpt High HIV area amox x 5 days Low HIV area amox x 3 days 2+ mo, severe amp or benzylpen PLUS gent ≥ 5 d 2+ mo, 2nd line ceftriaxone (80 mg/kg IM or IV daily) ≥ 5 d Amox 40 mg/kg/dose orally twice daily Amp 50 mg/kg/dose IM or IV every 6 h Benzylpenicillin 50,000 u/kg/dose IM or IV every 6 h Gent 7.5 mg/kg/dose IM or IV daily WHO Hospital Care for Children 2013 Lassi ZS Arch Dis Child 2014

30. Complicated Pneumonia (Effusion) Antibiotics (likely 3 weeks, parenteral for at least first week, then cloxacillin orally) Tap if > 1 cm fluid Drainage tube if persists Fibrinolytics if organized Video-Assisted Thoracoscopic Surgery if needed Thorax 66:815, 2011 WHO Hospital Care for Children 2013

31. Supportive Care for Child With Pneumonia Oxygen (for sat < 90%, excessive effort) Fear of Oxygen? Deal with It! Stevenson (Tanzania). Arch Dis Child 2014 Fluids and nutrition (IV vs NG vs oral) Analgesics (to decrease distress, for T> 39o C) It matters less what disease the patient has and more what patient has the disease. Hippocrates

32. Zinc for Pneumonia?

34. Zinc for Pneumonia? meta analysis 7 randomized controlled studies 1066 children < 5 yrs developing countries NO DIFFERENCE in severity or duration of illness Pediatr Resp Rev 13:184, 2012 94 children in Tanzania – NO EFFECT J Trop Pediatr 60:104-111, 2014

35. Why Do Kids Die of Pneumonia? Days of Illness Before Death 7 Hours of Illness Before Home Rx 4 Days of Illness Until Health Care 2 Days from First Treatment to Death 7 (2/3 of Deaths in Hospital) Problems: 1. Mistreatment with Anti-Malarials 2. Delays in Seeking Care 3. Low-Quality Care Uganda Bull World Health Organ 86:332, 2008

36. Tachypneaas a means of diagnosing “pneumonia” 2 - 12 months > 50 breaths / minute 12 - 60 months > 40 breaths / minute IF tachypnea (or severe retractions), give antibiotic. IF very sick, hospitalize for parenteral therapy.

37. A Common Situation A previously healthy ten week old presents with: 2 days of nasal congestion 1 day of cough and noisy breathing perhaps mild fever The exam shows: interactive child with rapid breathing and retractions coarse, wheezy breath sounds

38. RSV Bronchiolitis in Africa? Kilifi, Kenya

39. RSV Bronchiolitis in Kenya? Of 25,149 “under 5s” admitted ’02-’07 in Kilifi > 7359 (29%) had severe pneumonia > 15% with RSV (20% of those < 6 months) O.3% of under 5s hospitalized for RSV per year Of those admitted, 2% die Nokes DJ. Clinical Infectious Diseases 49:1341, 2009

40. Bronchiolitis in Thailand? 354 children 1-12 months old, Bangkok Lower Respiratory Tract Infection Influenza 7% RSV 29% especially July – October J Med Assoc Thai 94:S164, 2011

41. WHAT Causes Bronchiolitis? Respiratory Syncytial Virus (RSV) – esp 2-6 mo Human Metapneumovirus - identified 2001 similar illness to RSV but severe if co-infected Human Bocavirus – identified 2005 similar illness to RSV but severe if co-infected Rhinovirus – typically older than RSV kids Adenovirus, Coronavirus, Enterovirus Influenza Virus, Parainfluenza Virus Arch Dis Child 93:793, 2008 Arch Dis Child 95:35, 2010

42. The 10 Week Old Has Bronchiolitis.What Treatments Might Help?

43. The 10 Week Old Has Bronchiolitis.What Treatments Might Help? Supportive Care Fluids – possibly IV if tachypnea, poor feeding Nutrition Suction – temporary relief, deeper not helpful Oxygen– maybe keep O2 saturation > 89% Chest Physiotherapy – distress >> benefit Pediatrics 118:1774, 2006

44. Treatment of Child With Bronchiolitis Cough Suppression and/or Decongestants Not effective Some risk of toxicity NOT recommended JAMA 299:887, 2008, Pediatr Nurs 33:515, 2007

45. Treatment of Child With Bronchiolitis Albuterol/Salbutamol Several Studies Transient mild improvement in up to 25% Improvement not sustained No change in overall clinical course Maybe helpful if previous recurrent wheezing Pediatrics 118:1774, 2006; Arch Dis Child 93:793, 2008 Possible therapeutic trial??

46. Treatment of Child With Bronchiolitis Epinephrine/Adrenaline 194 infants hospitalized in Australia Nebulized epinephrine or saline three times Observed at admission, pre-dose, 30 & 60 min post-dose Increased HR after does of epinephrine No overall change in time to discharge readiness Longer stay required if epinephrine given to babies requiring oxygen and IV fluids N Engl J Med 349:27, 2003

47. Treatment of Child With Bronchiolitis Glucocorticoids (Steroids) 600 children 2-12 months old, US Dexamethasone (1mg/kg) vs placebo on arrival All improved over 4 hours No difference in need for admission, course No difference in condition after 4 hours New Engl J Med 357:331, 2007 Consistent with 13 other studies Cochrane Database Syst Rev 3:CD004878, 2004

48. Treatment of Child with Bronchiolitis Hypertonic Saline Nebulized 3% Saline versus 0.9% Saline Shorter Length of Stay by 0.94 days (p=0.0006) Lower Post-Inhalation Clinical Score for first three days of treatment (p<0.05) Cochrane Database Syst Rev 8;4:CD000458, 2008

49. Treatment of Child with Bronchiolitis Hypertonic Saline (with epinephrine) Nebulized 3% Saline versus 0.9% Saline Respiratory Distress NOT different Oxygen Saturations NOT different Admission Required NOT different Return to ED NOT different Arch Pediatr Adolesc Med 163:1007, 2009

50. Treatment of Child with Bronchiolitis Hypertonic Saline Conflicting Evidence Likely not helpful in emergency department Perhaps try in inpatient setting Grewal S et al. JAMA Pediatrics 168:607, 2014 Wu S et al. JAMA Pediatrics 168:657, 2014 Florin TA et al. JAMA Pediatrics 168:664, 2014