1、4/29/2019,Dr.HU Bijie,1,Respiratory Diseases Pneumonia 肺炎,Dr. Bijie HU（胡必杰） Zhongshan Hospital of Fudan University Shanghai,4/29/2019,Dr.HU Bijie,2,Semin Respir Infect 9(3):140-52，1994,mortality (per10 000),Mortality Trends with Pneumonia from 1900 to 1990 in USA,0,20,40,60,80,100,120,140,160,180,20
2、0,1900,1910,1920,1930,1940,1950,1960,1970,1980,1990,Pneumonia is not the “captain of death” anymore?,4/29/2019,Dr.HU Bijie,3,2002年9月歌手高枫因卡氏肺孢子虫肺炎（PCP）不治身亡,4/29/2019,Dr.HU Bijie,4,4/29/2019,Dr.HU Bijie,5,4/29/2019,Dr.HU Bijie,6,1990 2020 Cardiovascular disease Cerebrovascular diseases Lower respirato
3、ry infections Diarrhea Perinatal disease COPD Tuberculosis Morbilli Traffic accidents Lung cancer,Gastric cancer HIV suicide,Editorial, Lancet, 1997, 349: 1263.,Mortality Forecast by WHO,4/29/2019,Dr.HU Bijie,7,What is pneumonia?,To the pathologist an infection of the alveoli, distal airways, and in
4、terstitium of the lung increased weight of the lungs, consolidation alveoli filled with WBC, RBC, and fibrin To the clinician fever, chills, cough, pleuritic chest pain, sputum production, hyper- or hypothermia, increased respiratory rate, dullness to percussion, bronchial breathing, egophony, crack
5、les, wheezes, pleural friction rub opacity on chest radiography,4/29/2019,Dr.HU Bijie,8,Definition,Pneumonia is the inflammation of lower respiratory tracts including alveoli, interstitial tissues, and bronchiole by the microorganisms, chemical irritations or by an immunological process,4/29/2019,Dr
6、.HU Bijie,9,Classifications?,Lobar (segmental) lobular (bronchopneumonia)interstitial,4/29/2019,Dr.HU Bijie,10,Classifications & Terminology,Acute, subacute, chronic Bacterial, viral, fungal, parasitic (tuberculosis) Typical vs. Atypical (Mycoplasma, Chlamydia, Legionella) Ventilator Associated Pneu
7、monia (VAP)Nursing Home Acquired Pneumonia (NHAP)Health-care Associated Pneumonia (HCAP) Immune-compromised vs. immune-competentImmune-compromised Host Pneumonia (ICHP) Mild, moderate, severe Infections vs. noninfections Primary vs. Secondary,4/29/2019,Dr.HU Bijie,11,CAP vs HAP,community-acquired pn
8、eumonia treated in an ambulatory admission to the hospitalhospital-acquired pneumonia (nosocomial) ventilator-associated non-ventilator-associatedlong-term-care facilities (LTCFs),4/29/2019,Dr.HU Bijie,12,PATHOGENESIS,potential pathogen reach LRT in sufficient numbers or with sufficient virulence to
9、 overwhelm host defenses Possible routes gross aspiration anaerobic organisms and gram-negative bacilli microaspiration (oropharyngeal secretions colonized with pathogenic microorganisms)Streptococcus pneumoniae, Haemophilus influenzae aerosolization Mycobacterium tuberculosis, endemic fungi, Legion
10、ella spp., Coxiella burnetii, respiratory viruses (influenza viruses A, B) hematogenous spread from a distant infected site Staphylococcus aureus (MRSA) Escherichia coli direct spread from a contiguous infected site,4/29/2019,Dr.HU Bijie,13,Microbial Factors mechanisms to counteract host defenses Ho
11、st Factors Hypogammaglobulinemia defects in phagocytosis or ciliary function Neutropenia functional or anatomical asplenia reduction in CD4+ T lymphocyte counts Anatomical defects: obstructed bronchus, bronchiectasis,4/29/2019,Dr.HU Bijie,14,PATHOPHYSIOLOGY,Vital capacity, lung compliance, functiona
12、l residual capacity, and total lung capacity are below normal Ventilation-perfusion mismatch and intrapulmonary shunting are responsible for the hypoxemia,4/29/2019,Dr.HU Bijie,15,PATHOLOGY,Lobar Pneumonia Congestion, red hepatization, gray hepatization, resolution Bronchopneumonia a patchy consolid
13、ation involving one or several lobes Interstitial Pneumonia inflammatory process predominantly involving the interstitium, including the alveolar walls and the connective tissue around the bronchovascular tree Miliary Pneumonia Original: diffusely distributed 2- to 3-mm lesions of hematogenous tuber
14、culosis to millet seeds current: numerous discrete lesions resulting from the spread of the pathogen to the lungs via the bloodstream,4/29/2019,Dr.HU Bijie,16,PULMONARY COMPLICATIONS,necrotizing pneumonia formation of abscesses vascular invasion with infarction cavitation extension to the pleura emp
15、yema bronchopleural fistula other interstitial emphysema Pneumothorax ARDS fibrosis - organizing pneumonia, bronchiolitis obliterans pleural adhesions,4/29/2019,Dr.HU Bijie,17,Community-acquired Pneumonia,4/29/2019,Dr.HU Bijie,18,Epidemiology,Incidence 510/1,000/year 6th leading cause of death in U.
16、S. Number one among the infectious diseases 5.6 million patients annually in US Mortality OPD 1-5 % Inpatients 25% ICU 50-60%,4/29/2019,Dr.HU Bijie,19,Etiologic Agents of CAP,Carroll KC. 2002. J Clin Microbiol 40:3115-3120. Sharp SE, et.al. Cumitech 2003,4/29/2019,Dr.HU Bijie,20,Causative pathogens
17、in 5,961 adults admitted to hospital with CAP identified in 26 prospective studies from 10 European countries,Woodhead M. Chest 1998;183S-187S,4/29/2019,Dr.HU Bijie,21,Isolation Rates of Various Pathogens,Hu bijie, et al. Epidemiological Survey on the Pathogenic Spectrum of CAP in China, 2005,4/29/2
18、019,Dr.HU Bijie,22,259 Bacterial Strains Isolated from CAP,Bacteria name, # strains, proportion %,Hu bijie, et al. Epidemiological Survey on the Pathogenic Spectrum of CAP in China, 2005,4/29/2019,Dr.HU Bijie,23,Pathogens of Atypical Pneumonia,Legionella spp Mycoplasma pneumoniae Chlamydia pneumonia
19、e Chlamydia psittaci Coxiella burnetii Francisella tularensis PCP Pneumocystis carinii pneumonia Influenza A/B RSV respiratory syncytial virus CMV cytomegalovirus Adenovirus SARS Coronavirus SARS,File TM Jr, et al. Infect Dis Clin North Am. 1998;12:572. Levison ME. Harrisons Principles of Internal M
20、edicine. McGraw-Hill; 1998:1439. Bartlett JG, et al. Clin Infect Dis. 1998;26:821, Table 9.,4/29/2019,Dr.HU Bijie,24,Proportion of Atypical Pathogens in CAP,Hu bijie, et al. Epidemiological Survey on the Pathogenic Spectrum of CAP in China, 2005,4/29/2019,Dr.HU Bijie,25,Manifestation,Systematic ofte
21、n preceded by a URI sudden onset, shaking chill, Fever other: nausea, vomiting, malaise, and myalgias Local pain with breathing on the affected side (pleurisy) Cough：(dry initially but usually becomes productive, dyspnea, and sputum production） Sign T: 38 40.5; pulse is usually 100 to 140 beats/min;
22、 respirations accelerate to 20 to 45 breaths/min. lobar consolidation; crackles; pleural effusion,4/29/2019,Dr.HU Bijie,26,Independent risk factors,alcoholism (RR 9) asthma (RR 4.2) immunosuppression (RR 1.9) age of 70 years (RR 1.5 vs. an age of 60 to 69 years) pneumococcal pneumonia: dementia, sei
23、zures, congestive heart failure, cerebrovascular disease, tobacco smoking, alcoholism, COPD, HIV Legionnaires disease: male gender, current tobacco smoking, diabetes, hematologic malignancy, cancer, end-stage renal disease, and HIV infection GNB: probable aspiration, previous hospital admission, pre
24、vious antimicrobial Rx, bronchiectasis, heavy drinkers,4/29/2019,Dr.HU Bijie,27,Modifying factors that increase the risk of infection with specific pathogens,4/29/2019,Dr.HU Bijie,28,General Lab Examinations,Blood tests：leukocytosis with a shift to the left hypoxemia respiratory alkalosis,4/29/2019,
25、Dr.HU Bijie,29,4/29/2019,Dr.HU Bijie,30,DiagnosisClinical,Fever380 C New cough, sputum, hemoptysis+Pleuritic chest pain WBC10109 or 4109 Rales, rhonci, wheezing New or evolving infiltrate on chest radiograph High-resolution computed tomography (CT),4/29/2019,Dr.HU Bijie,31,Medical Imaging,Chest Plai
26、n X-ray film (CXR) Computed Tomography (CT) scan infiltrate, consolidation, bronchograms Ultrasound Imaging Magnetic resonance imaging (MRI),4/29/2019,Dr.HU Bijie,32,4/29/2019,Dr.HU Bijie,33,Diagnosis Microbiological,Pleural fluid & blood Sputum stains and culture:(washing, quantitation, cytological
27、 screening) collected by expectoration Similar: by nasotracheal, orotracheal aspirate Lower respiratory secrets (LRT sterile but URT, mouth and nose, colonised by large numbers of different bacteria) Transtracheal aspiration,TTA Endotracheal aspiration, ETA Protected specimen brush, PSB Bronchial al
28、veolar lavage, BAL Lung aspiration, LA,4/29/2019,Dr.HU Bijie,34,Grams stain of expectorated sputum,Sensitivity and specificity vary widely Cytological screening 25 neutrophils and 10 squamous epithelial cells per low power field not evaluated for Legionella, mycobacteria or viral infections Direct s
29、taining diagnostic for Mycobacterium sp. Endemic fungi Legionella sp. (DFA stain) P. carinii,4/29/2019,Dr.HU Bijie,35,4/29/2019,Dr.HU Bijie,36,DETECTION OF ANTIGENS OF PULMONARY PATHOGENS IN URINE L. pneumophila serogroup 1 antigen S. pneumoniae urinary antigen SEROLOGYM. pneumoniaeC. pneumoniaeChla
30、mydia psittaciLegionella spp.C. burnetii adenovirus, parainfluenza viruses, influenza virus A. POLYMERASE CHAIN REACTION DNA of Legionella spp., M. pneumoniae, and C. pneumoniae,4/29/2019,Dr.HU Bijie,37,TREATMENT,SITE OF CARE ANTIBIOTIC THERAPY SWITCH FROM INTRAVENOUS TO ORAL ANTIBIOTIC THERAPY DURA
31、TION OF ANTIBIOTIC THERAPY,4/29/2019,Dr.HU Bijie,38,Associated Mortality by Age and Treatment,Age Mortality 18-64 yr 10% - 15% 65-74 yr 20% 75-84 yr 30% 85 yr 40% Untreated 50% - 90%,4/29/2019,Dr.HU Bijie,39,Patient Points characteristics assigned Demographic factorsAge: males age (in yrs) females a
32、ge (in yrs) -10 Nursing home resident +10 Comorbid illnessesNeoplastic disease +30Liver disease +20Congestive heart failure +10Cerebrovascular disease +10Renal disease +10,Physical examination findingsAltered mental status +20Respiratory rate 30/min +20Systolic blood pressure 125 / min +10Laboratory
33、 findingspH 10.7 mmol/L +20Sodium 13.9 mmol/L +10Hematocrit 30% +10PO2 60 mmHg +10Pleural effusion +10,Prediction model for CAP,Fine MJ, et al. NEJM 1997;336(4)243-250,4/29/2019,Dr.HU Bijie,40,Risk-Class Mortality Rates for Patients with Pneumonia,Risk No. of Mortality Recommendations class No. of p
34、oints patients (%) for site of care I No predictors 3,304 0.1 Outpatient II 130 9,333 29.2 Inpatient,Fine MJ, et al. NEJM 1997;336(4)243-250,4/29/2019,Dr.HU Bijie,41,Meehan TP, et al. JAMA 1997;278:2080-2084.,Pneumonia MQIS Project,4/29/2019,Dr.HU Bijie,42,Group I: Outpatients, No cardiopulmonary di
35、sease, no modifying factors,4/29/2019,Dr.HU Bijie,43,Group II: Outpatient, with cardiopulmonary disease, and/or other modifying factors,4/29/2019,Dr.HU Bijie,44,Penicillin-Nonsensitive Streptococcus Pneumoniae in USA,4/29/2019,Dr.HU Bijie,45,4/29/2019,Dr.HU Bijie,46,Penicillins MIC Distribution in 7
36、7 Strains of S. Pneumonia,PSSP=71.4% PISP =19.5% PRSP= 9.1%,4/29/2019,Dr.HU Bijie,47,Group IIIa: Inpatients, cardiopulmonary disease and/or modifying factors,4/29/2019,Dr.HU Bijie,48,Group IIIb: Inpatients, no cardiopulmonary disease, no modifying factors,4/29/2019,Dr.HU Bijie,49,Severe Community Ac
37、quired Pneumonia,one major criteria Need for Mechanical Ventilation; incresing infiltration 50% within 48 hours Septic shock, need for vasopressors Renal failure two minor criteria Respiratory rate 30/min PaO2/FiO2 ratio 250mmHg Diffuse bilateral involvement or multiple lobes B.P. 90 mmHg systolic B
38、.P. 60 mmHg diastolic,4/29/2019,Dr.HU Bijie,50,GROUP IVa: ICU-admitted, no risks for pseudomonas aeruginosa,4/29/2019,Dr.HU Bijie,51,Rx for AP: In Vitro Activity MIC Ranges (g/mL),File TM Jr, et al. Infect Dis Clin North Am. 1998;12:585,Doxycycline 0.25 0.06-0.25 0.8 Tetracycline 0.25 0.06-0.125 Cip
39、rofloxacin 2.0 1.0 0.12-0.5 Ofloxacin 2.0 1.0 0.06-0.25 Levofloxacin 0.5 0.5 0.125 Grepafloxacin 0.25 0.5 0.016 Sparfloxacin 0.06 0.25 0.06,4/29/2019,Dr.HU Bijie,52,GROUP IVb: ICU-admitted, risks for pseudomonas aeruginosa,4/29/2019,Dr.HU Bijie,53,Modifying factors that increase the risk of infectio
40、n with specific pathogens,4/29/2019,Dr.HU Bijie,54,Duration of therapy,S pneumoniae: until afebrile for 3-5d C pneumoniae:7-14 d M pneumoniae: not well established. Legionella: 10-21 d S aureus, P aeruginosa: 1014d Klebsiella: 710d anaerobes ?,4/29/2019,Dr.HU Bijie,55,Prophylaxis,Vaccine containing
41、the 23 specific polysaccharide antigens of the pneumococcus types (account for 85 to 90%) recommended for children 2 yr and adults at increased risk for pneumococcal disease or its complications; older adults duration of protection: 5 yr (revaccinated in 5 yrs tend to have a more intense local react
42、ion),4/29/2019,Dr.HU Bijie,56,Hospital-acquired Pneumonia,4/29/2019,Dr.HU Bijie,57,Site Distribution in Adult ICUs Major Types of Infection (NNIS data, 1992-1997),4/29/2019,Dr.HU Bijie,58,Nosocomial Infections, USA Then and Now,*Among surgical patients; inpt. surgical procedures decreased from 18.3
43、M to 13.3 M.,Weinstein, Emerg Inf Dis 1998;4:416-20.,4/29/2019,Dr.HU Bijie,59,Epidemiology：“3 high”,High Morbidity：5-10 per 1000；Incidence increases by 6-20 fold in VM； High Mortality：leading cause of death due to HAI；crude rate 30-50%； High Cost： 1 billion dollars/year in US. Hospital stay increase
44、s by 7-9 days ；,4/29/2019,Dr.HU Bijie,60,Pathogenesis,Invasion of the lower respiratory tract by: Aspiration of oropharyngeal/GI organisms Inhalation of aerosols containing bacteria Hematogenous spread,4/29/2019,Dr.HU Bijie,61,Colonization Aspiration,HAP,MRSA*,4/29/2019,Dr.HU Bijie,62,Acinetobacter
45、only infects highly debilitated patients With relatively low mortality 8-12% H. Richet ICAAC 2004 Abstract #403,No antibiotics in case of colonization,4/29/2019,Dr.HU Bijie,63,Risk Factors,Host Factors Extremes of age, severe illnesses, immunosupression, coma, alcoholism, malnutrition, COPD, DM Enha
46、nce oropharynx and stomach colonization ICU, antibiotics, endotracheal intubation, etc. Favoring aspiration or reflux Supine position, depressed consciousness, endotracheal intubation, insertion of nasogastric tube Mechanical ventilation Impaired mucociliary, secretion pooling in subglottic area, co
47、ntaminated equipment and hands of HCWs Impede adequate pulmonary toilet Head and neck surgery, trauma, sedation etc.,4/29/2019,Dr.HU Bijie,64,Etiologic Agents,S.aureus Enterobacteriaceae P.aeruginosa Acinetobacter sp. Polymicrobial Anaerobic bacteria Legionella sp. Aspergillus sp. Viral,4/29/2019,Dr
48、.HU Bijie,65,Etiologic Agents,Mild to moderate HAP or early severe HAP Streptococcus pneumoniae Haemophilus influenza MSSA Klebsiella Pneumoniae Enterobacter, E coli, Proteus, Serratia Severe HAP Pseudomonas Acinetobacter MRSA,4/29/2019,Dr.HU Bijie,66,Bugs of Hosp-acquired pneumonia,4/29/2019,Dr.HU
49、Bijie,67,Diagnosis,Clinical fever; cough with purulent sputum Radiographic new or progressive infiltrates on CXR, Laboratorial leukocytosis or leukopenia Microbiologic Suggestive gram stain and positive cultures of sputum, tracheal aspirate, BAL, PSB, pleural fluid or blood Quantitative cultures,4/29/2019,Dr.HU Bijie,68,Differential diagnosis,
