Pneumonia Pathophysiology and Clinical Manifestations J Matthew Velkey

Pneumonia: Pathophysiology and Clinical Manifestations J. Matthew Velkey, Ph. D Department of Cell Biology Duke University School of Medicine Andrew Alspaugh, MD Department of Medicine Infectious Disease Division Duke University School of Medicine 2

Learning Objectives • • • Recognize the epidemiology and morbidity of pneumonia Define pneumonia and types of lower respiratory tract infections Understand features involved in the pathophysiology of pneumonia Recognize the entity known as Community Acquired Pneumonia (CAP) Appreciate the spectrum of pneumonia clinical presentation Identify common complications of pneumonia 3

Pneumonia is common and serious • 5. 6 million cases in US in 2011(1) • 2 nd leading cause of hospitalization in US (1. 1 million admissions in US)(1) ~20% of patients with pneumonia require hospitalization • 6 th leading cause of death in US in 2011 (~60, 000 deaths)(1) ~10% of patients with pneumonia die Variations in rates of disease: • • • (1) Higher rates in winter months • More common in men More common in African Americans compared to Caucasians More common in children and older adults (overall rate for 18 -49 yo is ~5 per 1000 overall rate for >65 yo is 75 per 1000 ) Anevlavis S; Bouros D (2010). Expert Opin Pharmacother 11 (3): 361– 74. 4

Lower respiratory and pleural disease Empyema: purulent exudate in the pleural cavity Pneumonia -- infection of alveoli (viral or bacterial) vs. Pneumonitis -- immune-mediated inflammation of alveoli Bronchitis -- inflammation of bronchi, may be immunemediated, e. g. asthma, COPD, or infectious (usually viral but can be bacterial) Abscess: circumscribed collection of pus within the lung parenchyma Bronchiolitis: inflammation of bronchioles (often viral but can be bacterial) 5

PNEUMONIA: CLEARANCE vs. COLONIZATION Microbes constantly enter airways but many factors prevent colonization: • mucous entrapment • ciliary clearance • immune surveillance • intact epithelial barrier • secreted factors such as: ‒ secretory Ig. A ‒ surfactant proteins (SP-a, SP-d) ‒ defensins Disrupting or overwhelming these defense mechanisms can allow microbes to colonize the lungs, resulting in PNEUMONIA 6

Factors favoring colonization Disruption of mucociliary clearance: • airway obstruction (CF, COPD, chronic bronchitis, neoplasm) • ciliary dysfunction (Kartagener, smoking, ciliostatic factors) Disruption of intact epithelial barrier: • injury (e. g. pulmonary edema, intubation) or infection (e. g. viral respiratory infection such as influenza) Increasing “inoculation” events: • • • altered consciousness debility dysphagia intubation bacteremia Decreasing immune function: • immune suppression (transplant, HIV) • evading host immunity (Ig. A proteases, encapsulation) 7

Effects and patterns of microbial colonization: where and how i nflam m ation appears can be inf ormat ive Alveolar • In alveolar lumen • Purulent exudate of RBCs and PMNs Interstitial • Mostly in alveolar wall • Mononuclear WBCs • Fibrinous exudate Lobar pneumonia • lobar distribution • “typical” CAP • S. pneumo, H. flu. Bronchopneumonia • patchy distribution • aspiration, intubation, bronchiectasis • Staph, enterics, Pseudomonas Atypical pneumonia • diffuse infiltrate w/ perihilar concentration • Mycoplasma, Chlamydophila, Legionella • Respiratory viruses, e. g. influenza 8

Community-Acquired Pneumonia • Infection of the pulmonary parenchyma acquired from exposure in the community • Classically divided into “typical” and “atypical” syndromes: I. “Typical” CAP: • presents with “typical” severe, acute infection • infectious agent (usually S. pneumo or H. flu) is culturable/ identifiable • responsive to cell-wall active antibiotics II. “Atypical” CAP: • presentation is usually sub-acute • causative pathogens are difficult to culture/identify by standard methods • not responsive to penicillins 9

Typical CAP presentation History • Previously healthy with sudden onset of fever and shortness of breath Physical signs and symptoms • • • fever tachycardia tachypnea productive cough with purulent sputum and possible hemoptysis pallor and cyanosis localized: − dullness to percussion − decreased breath sounds − crackles , ronchi , egophony (“E” -to-”A” change) Investigations • • • CXR showing lobar consolidation CBC showing leukocytosis w/ left shift Sputum sample contains neutrophils, RBCs; Gram stain may be positive depending on organism 10

Typical CAP presentation History • Previously healthy with sudden onset of fever and shortness of breath Physical signs and symptoms • • • fever tachycardia tachypnea productive cough with purulent sputum and possible hemoptysis pallor and cyanosis localized: − dullness to percussion − decreased breath sounds − crackles, ronchi, egophony (“E-to-A” change) Investigations • • • CXR showing lobar consolidation CBC showing leukocytosis w/ left shift Sputum sample contains neutrophils, RBCs; Gram stain may be positive depending on organism 11

Typical CAP presentation History • Previously healthy with sudden onset of fever and shortness of breath Physical signs and symptoms • • • fever tachycardia tachypnea productive cough with purulent sputum and possible hemoptysis pallor and cyanosis localized: − dullness to percussion − decreased breath sounds − crackles, ronchi, egophony (“E-to-A” change) Investigations • • • CXR showing lobar consolidation CBC showing leukocytosis w/ left shift Sputum sample contains neutrophils, RBCs; Gram stain may be positive depending on organism 12

Atypical CAP Presentation • 32 YO healthy patient – one week of low grade fever, sore throat, and intractable cough • Minimal sputum production • Able to continue to work • No sick contacts, recent travel, or evidence of altered immune system • PE reveals a mildly ill-appearing patient with diffuse wheezes on lung exam • Primary care physician prescribes empiric antibiotics for CAP with complete resolution • “Walking pneumonia” syndrome 13

Complications of pneumonia Pleural effusion • inflammation leads to exudation of fluid into pleural space • can compromise lung function Empyema • purulent exudate in pleural space • necrosis/breakdown of visceral pleura and/or spread of infection into pleura Pleural adhesions, lung fibrosis 14

Complications of pneumonia Abscess / cavitary lesion • circumscribed focus of liquefactive necrosis within lung tissue • associated with necrotizing Staph or Strep infections or Gram-neg rods (e. g. aspiration) 15

C r e d i t s : Pneumonia Location of item (slide #5): "Respiratory system complete no labels" by Bibi Saint-Pol en. wikipedia. org/wiki/File: Respiratory_system_complete_en. svg. Licensed under CC BY-SA 3. 0 via Wikimedia Commons http: //commons. wikimedia. org/wiki/File: Respiratory_system_complete_no_labels. svg#/media/File: Respiratory_system_com plete_no_labels. svg Location of item (slide #5): "Diagram showing a build up of fluid in the lining of the lungs (pleural effusion) CRUK 054" by Cancer Research UK - Original email from CRUK. Licensed under CC BY-SA 4. 0 via Wikimedia Commons http: //commons. wikimedia. org/wiki/File: Diagram_showing_a_build_up_of_fluid_in_the_lining_of_the_lungs_(pleural_effusi on)_CRUK_054. svg#/media/File: Diagram_showing_a_build_up_of_fluid_in_the_lining_of_the_lungs_(pleural_effusion)_CRUK _054. svg Location of item (slide #5): Bronchitis illustration: http: //commons. wikimedia. org/wiki/File: Bronchitis. jpg -- This work is in the public domain in the United States because it is a work prepared by an officer or employee of the United States Government as part of that person’s official duties under the terms of Title 17, Chapter 1, Section 105 of the US Code. Location of item (slide #6): color illustration of upper and lower airway anatomy. Blausen. com staff. "Blausen gallery 2014". Wikiversity Journal of Medicine. DOI: 10. 15347/wjm/2014. 010. ISSN 20018762. - Own work Location of item (slide #6): illustration of upper airway defense mechanisms. http: //openi. nlm. nih. gov/detailedresult. php? img=59560_rr 25 -1&req=4. Figure 1 from Bals, R. Epithelial antimicrobial peptides in host defense against infection. Respir Res. 2000; 1: 141 -50. doi: 10. 1186/rr 25 16

C r e d i t s ( c o n t i n u e d ) : Pneumonia Location of item (slide #6): illustration of alveolar defense mechanisms. http: //www. nature. com/nri/journal/v 5/n 1/fig_tab/nri 1528_F 1. html. Figure 1 from Wright, JR. Immunoregulatory functions of surfactant proteins. Nat Rev Immunol. 2005; 5: 58 -68. doi: 10. 1038/nri 1528 Location of item (slide #7): color illustrations of alveolar and interstitial inflammation, lobar, bronchial, and interstitial patterns of pneumonia. http: //quizlet. com/27416956/pulmonary-pathology-and-pathophysiology-flash-cards/. Contributors to Quizlet. com warrant that the downloading, copying and use of the content will not infringe the proprietary rights, including but not limited to the copyright, patent, trademark or trade secret rights, of any third party. Location of item (slide #7 and slide #12): chest x-ray of lobar pneumonia. http: //biomarker. cdc. go. kr/biomarker/diseaseimg/pneumonia-Community_acquired. jpg Location of item (slide #7): chest x-ray of bronchopneumonia. http: //www. ebmedicine. net/topics. php? paction=show. Topic. Seg&topic_id=118&seg_id=2306 Location of item (slide #7): chest x-ray of interstitial (atypical) pneumonia. http: //www. ebmedicine. net/topics. php? paction=show. Topic. Seg&topic_id=118&seg_id=2306 Location of item (slide #11): illustration of CAP patient. RWJF Pneumonia Module Springboard Video. 17

C r e d i t s ( c o n t i n u e d ) : Pneumonia Location of item (slide #11): crackles sound clip: http: //en. wikipedia. org/wiki/File: Crackles_pneumonia. O. ogg; ronchi sound clip: http: //www. easyauscultation. com/cases? coursecaseorder=5&courseid=201; normal “E” lung sound: http: //www. easyauscultation. com/cases? coursecaseorder=4&courseid=202; egophony lung sound (“E” to “A” change): http: //www. easyauscultation. com/cases. aspx? coursecaseorder=5&courseid=202 Location of item (slide #13): Gram Stain of a film of sputum from a case of lobar pneumonia. CDC Location of item (slide #14 & 15): Chest X-ray of atypical pneumonia. Dr. Mike Malinzak. Duke University. Dept. of Radiology. Location of item (slide #16): Chest X-ray of HAP. Dr. Mike Malinzak. Duke University. Dept. of Radiology. Location of item (slide #17): "Diagram showing a build up of fluid in the lining of the lungs (pleural effusion) CRUK 054" by Cancer Research UK - Original email from CRUK. Licensed under CC BY-SA 4. 0 via Wikimedia Commons http: //commons. wikimedia. org/wiki/File: Diagram_showing_a_build_up_of_fluid_in_the_lining_of_the_lungs_(pleural_effusion)_CRU K_054. svg#/media/File: Diagram_showing_a_build_up_of_fluid_in_the_lining_of_the_lungs_(pleural_effusion)_CRUK_054. svg Location of item (slide #18): "CT chest in pneumonia with abscesses caverns and effusions d 0" by Christaras A - Own work from anonmyized dicom image. Licensed under CC BY 2. 5 via Wikimedia Commons http: //commons. wikimedia. org/wiki/File: CT_chest_in_pneumonia_with_abscesses_caverns_and_effusions_d 0. jpg#/media/File: CT_ch est_in_pneumonia_with_abscesses_caverns_and_effusions_d 0. jpg Location of item (slide #18): "Abscess" by Yale Rosen - http: //www. flickr. com/photos/pulmonary_pathology/3679097009/. Licensed under CC BY-SA 2. 0 via Wikimedia Commons - http: //commons. wikimedia. org/wiki/File: Abscess. jpg#/media/File: Abscess. jpg 18