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PATOLOGIA DO APARELHO RESPIRATÓRIO Carlos Robalo Cordeiro Pneumonias

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Page 1: Pneumonia 1

PATOLOGIA DO APARELHO RESPIRATÓRIO

Carlos Robalo Cordeiro

Pneumonias

Page 2: Pneumonia 1

O termo pneumonia, do ponto de vista etimológico, deriva da noção de infecção pulmonar por pneumococo- Streptococcus pneumoniae.

Pneumonia

todo o processo infeccioso dos espaços alveolares ou do parênquima pulmonar, com substituição do seu conteudo aéreo por células inflamatórias e secreções

Ambulatório

sintomas de Infecção.R.aguda

sinais focais no exame objectivo

queixas sistémicas

ausência de outra explicação

Page 3: Pneumonia 1

Pneumonia

Hospitalar

sintomas e sinais de Infecção.R.aguda

+

alterações radiológicas

In THORAX 2001, 56, (suppl4)- BTS GUIDELINES 2001

Page 4: Pneumonia 1

Classificação

radiológica

segmentareslobaresintersticiais

broncopneumonia histológica

alveolaresintersticiais

etiológicabacterianavirusalfúngica

tipo de evoluçãoagudassubagudascrónicas

Classificação

epidemiológica

PACPN/PHP.

Imunodeprimido

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Epidemiologia

Maioria tratada em ambulatório

0- 42 % requerem hospitalização

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Epidemiologia

Incidência 5- 11/ 1000/ ano UK

4 Milhões de casos/ano

60.000 mortes/ ano

PAC é uma importante causa de mortalidade 4-12 %

D. internados

In THORAX 2001, 56, (suppl4)- BTS GUIDELINES 2001

Page 7: Pneumonia 1

• 30- 60 % impossível identificar

• agente etiológico varia consoante:

- área geográfica

- idade

- patologias associadas

DPOC

Patologia CV

DM

Lar

Alcoolismo

CT

Etiologia

Page 8: Pneumonia 1

Etiologia

• Streptococcus pneumoniae 20- 60 %

• Haemophilus influenza 3- 10

• Chlamydea pneumoniae 5- 17

• Vírus 2- 15

• anaeróbios 6- 10

• gram - 3- 10

• S. Aureus 3- 5

• L. Pneumophila 2- 8

• M. Catarrhalis 1- 3

In CHEST/115/3/ MARCH, 1999

Page 9: Pneumonia 1

Penicillin-resistant and drug-resistant pneumococci

  Age > 65 yr

  B-Lactam therapy within the past 3 mo

  Alcoholism

  Immune-suppressive illness

  Multiple medical comorbidities

  Exposure to a child in a day care center

Enteric gram-negatives

  Residence in a nursing home

  Underlying cardiopulmonary disease

  Multiple medical comorbidities

  Recent antibiotic therapy

Pseudomonas aeruginosa

  Structural lung disease (bronchiectasis)

  Corticosteroid therapy (> 10 mg of prednisone per day)

  Broad-spectrum antibiotic therapy for > 7 d in the past month

  Malnutrition

Factores que aumentam o risco de infecção por agentes específicos

In AJCCRM- ATS Guidelines

Page 10: Pneumonia 1

• febre

• tosse

• expectoração purulenta

• dor torácica pleurítica

• dispneia

• alteração estado geral

• odinofagia

• mialgias

• náuseas/ vómitos

Clínica

• exame objectivo

auscultação

palpação

percussão

• ECD

H

BQ

GSA

Radiologia

Page 11: Pneumonia 1

• clínica

• exame objectivo

• radiologia

confirmação DX

localização

extensão

complicações

Diagnóstico

• radiologia

p. alveolar

p. broncopneumónico

p. intersticial

Page 12: Pneumonia 1

Diagnóstico- radiologia

• padrão alveolar

Imagem de condensação homogénea de limites mal definidos

Broncograma aéreo

Distribuição segmentar ou lobar

• padrão broncopneumónico

Distribuição segmentar

Aspecto algodonoso e multifocal, podendo coalescer

• padrão intersticial

Opacidades lineares, reticulo-micronodular

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Consolidação do lobo inferior direito

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• Exmes laboratoriais

Exame directo

Cultura

Hemograma

Bioquímica

GSA

Hemoculturas

Serologia VIH

Serologias específicas

Diagnóstico

Page 17: Pneumonia 1

Pneumonia Típica // Atípica ???

- Apresentação clínico-radiológica diferente ?

- sobreposição de achados ?

- AB b- lactâmicos ineficazes

- meios de diagnóstico específicos

- terapêutica diferente

Page 18: Pneumonia 1

Pneumonia Atípica

- etiologia:

Mycoplasma pneumoniae

Chlamydia pneumoniae

Chlamydia psitacci

Legionella pneumophila

Coxiella burnetti

Page 19: Pneumonia 1

Pneumonia Atípica

- início mais gradual

- tosse irritativa

- contexto epidémico/ epidemiológico

- manifestações extrapulmonares

mialgias

conjuntivite

exantema

diarreia

dor abdominal

vómitos

- padrão radiológico intersticial

- dissociação clínico- radiológica

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Tratamento

Estratificação de doentes

Grupo 1

ambulatório

sem factores modificadores

Grupo 2

ambulatório

com doença cardio-pulmonar

outros factores modificadores

Grupo 3

D. Internados

Grupo 4

D. Internados UCI In AJCCRM 2001, 163- ATS Guidelines

Page 23: Pneumonia 1

Grupo 1

Organisms Therapy

Streptococcus pneumoniae Advanced generation macrolide:   

azithromycin or clarithromycin  or

Doxycycline

or  amoxicillin/clavulanate

Mycoplasma pneumoniae

Chlamydia pneumoniae

Hemophilus influenzae

Respiratory viruses

Miscellaneous

Legionella spp.

Mycobacterium tuberculosis

Endemic fungiIn AJCCRM 2001, 163- ATS Guidelines

Nova FQ

Page 24: Pneumonia 1

Grupo 2 Ambulatório Cardio pulmonar/ F. modificadores

Organisms Therapy

Streptococcus pneumoniae

Mycoplasma pneumoniae

Chlamydia pneumoniae

Mixed infection (bacteria plus   atypical pathogen or virus)

Hemophilus influenzae

Enteric gram-negatives

Respiratory viruses

MiscellaneousMoraxella catarrhalis, Legionella spp.,

  aspiration (anaerobes), Mycobacterium

  tuberculosis, endemic fungi

B-Lactam (oral cefpodoxime,   cefuroxime,   HD amoxicillin,

  amoxicillin/clavulanate;or   parenteral ceftriaxone

  followed by oral   cefpodoxime)

plus

Macrolide or doxycycline

Or

Antipneumococcal

fluoroquinolone   (used alone)

In AJCCRM 2001, 163- ATS Guidelines

Page 25: Pneumonia 1

Grupo 3 D. internados

Organisms Therapy

a. Cardiopulmonary Disease and/or Modifying Factors

Streptococcus pneumoniae

Hemophilus influenzae

Mycoplasma pneumoniae

Chlamdia pneumoniae

Mixed infection

(bacteria   plus atypical pathogen)

Enteric gram-negatives

Aspiration (anaerobes)

Viruses

Legionella spp.

Miscellaneous

  Mycobacterium tuberculosis,

endemic     fungi, Pneumocystis

carinii

Intravenous B-lactam  (cefotaxime,

cefuroxime,ceftriaxone,

  ampicillin/sulbactam,   high-dose ampicillin)

plus

Intravenous or oral macrolide   or

doxycycline

or

Iv antipneumococcal   fluoroquinolone alone

In AJCCRM 2001, 163- ATS Guidelines

Page 26: Pneumonia 1

Grupo 3 D. internados

b. No cardiopulmonary Disease, No Modifying Factors

S. Pneumoniae

H. influenzae

M. pneumoniae

C. pneumoniae

Mixed infection (bacteria  plus atypical pathogen)

Viruses

Legionella spp.

Miscellaneous

  M. tuberculosis, endemic fungi,

P. carinii

Intravenous azithromycin alone. 

If macrolide allergic   or intolerant:   

Doxycycline  and a B-lactam

or

Monotherapy with an   

antipneumococcal   fluoroquinolone

In AJCCRM 2001, 163- ATS Guidelines

Page 27: Pneumonia 1

Duração do tratamento

• variável 7-14 D

• aparecimento de fármacos com maior semivida tecidular

• considerar:

doenças associadas

gravidade da doença

evolução da doença

agente etiológico

• M. Pneumoniae 10-14 D

C. Pneumoniae

• Legionella 14 DIn AJCCRM 2001, 163- ATS Guidelines

Page 28: Pneumonia 1

Reports of respiratory infection, WHO global surveillance networks, 2002–2003

• 27 November – Guangdong Province, China: Non-official report of outbreak of

respiratory illness with government recommending isolation of anyone

with symptoms (GPHIN)

• 11 February– Guangdong Province, China: Non-official report of health worker

outbreak of atypical pneumonia with high mortality (e-mail)

• 14 February– Guangdong Province, China: Official confirmation of outbreak of

atypical pneumonia with 305 cases and 5 deaths (China)

• 19 February– Hong Kong, SAR China: Official report of 33-year male and 9 year old

son in Hong Kong with Avian influenza (H5N1), source linked to Fujian

Province, China (FluNet)

Fonte: OMS D. Heymann

Page 29: Pneumonia 1

Intensified surveillance for pulmonary infections, WHO, 2003

• 26 February

– Hanoi, Viet Nam: Official report of 48-year-old business man with high

fever

(> 38 ºC), atypical pneumonia and respiratory failure with history of

previous travel to China and Hong Kong (Viet Nam)

• 4 March

– Hong Kong, SAR China: Official report of 77 medical staff from Kwong

Wah Hospital reported with atypical pneumonia (Hong Kong, SAR)

• 5 March

– Hanoi, Viet Nam: Official report of 7 medical staff from French Hospital

reported with atypical pneumonia (Viet Nam)

• 8 March

– WHO teams arrive Hong Kong and Hanoi, and with governments begin

investigation and containment activities Fonte: OMS D. Heymann

Page 30: Pneumonia 1

SARS Global Alert: 15 March 2003

• Atypical pneumonia with rapid progression to respiratory failure

• Health workers appeared to be at greatest risk

• Unidentified cause, presumed to be an infectious agent

• Antibiotics and antivirals did not appear effective

• Spreading internationally within Asia and to Europe and North

America

Fonte: OMS D. Heymann

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SARS Síndroma respiratória aguda

Alerta global

• Casos iniciais:

China

Vietnam

Indonésia

Filipinas

Singapura

• descohecimento do agente etiológico

• mortalidade

Page 32: Pneumonia 1

156 closecontactsof HCW

and patients

Index case from

Guangdong

Index case from

Guangdong

Hospital 2Hong Kong

4 HCW +2

Hospital 2Hong Kong

4 HCW +2

Hospital 3Hong Kong

3 HCW

Hospital 3Hong Kong

3 HCW

Hospital 1Hong Kong

99 HCW

Hospital 1Hong Kong

99 HCW

Canada12 HCW +

4

Canada12 HCW +

4

Hotel M.Hong Kong

IrelandIreland

USAUSA

New YorkNew York

Singapore34 HCW +

37

Singapore34 HCW +

37

Viet Nam37 HCW +

?

Viet Nam37 HCW +

?

BangkokHCW

BangkokHCW

4 otherHong Konghospitals28 HCW

4 otherHong Konghospitals28 HCW

Hospital 4Hong KongHospital 4

Hong Kong

B

I

K

F G

ED

CJ

H

A

SARS: chain of transmission among guests at Hotel Metropole, Hong Kong, 21 February

GermanyHCW +

2

GermanyHCW +

2

Source: WHO/CDC

D. Heymann

Page 33: Pneumonia 1

SARS: number of probable cases by date of report worldwide*, 1 March–5 May 2003

Date of report0

50

100

150

200

250

300

350

400

1-Mar-03 8-Mar-03 15-Mar-03 22-Mar-03 29-Mar-03 5-Apr-03 12-Apr-03 19-Apr-03 26-Apr-03 3-May-03

nu

mb

er o

f ca

ses

(n = 5 393)

* Includes all cases from Hong Kong SAR, Macao SAR and Taiwan, China, but only those cases elsewhere in China reported after 3 April 2003 (1,190 cases between 16 November 2002 and 3 April 2003 not shown). The United States of America began reporting probable cases of SARS to WHO on 20 April 2003.

Fonte: OMS D. Heymann

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Severe Acute Respiratory Syndrome (SARS): Global Alert, Global Response

World Health Organization

K. Stohr

Page 38: Pneumonia 1

SARS Epidemiology 1

• Routes of transmission

– Mainly droplet; person-to-person

– Virus excreted through respiratory secretions, stool, urine,

tears

– Fomites

• Incubation period

– Average: 2-7 d

• Case fatality rate

– Hong Kong: around 15%;

Fonte:K. Stohr. WHO

Page 39: Pneumonia 1

SARS Epidemiology 2

• Virus excretion

– Begins with onset of clinical signs (perhaps earlier)

– Respiratory tract

• Appears to peak around day 5; continues throughout the

disease

– day 10: 95%; day 13: 90%, day 19: 75%; day 21: 47%

– Stool

• Begins as early as day 3; shedding up to 10log6;

– Day 10: 100%; day 16:95%; day 19: 80%; day 21:

67%)Fonte:K. Stohr. WHO

Page 40: Pneumonia 1

SARS Diagnosis Summary

• Virus and Ab detection tests available

• Test are reliable in scientific laboratories

• Invaluable in understanding the epidemiology of the disease

• Limited use for case management and infection control

– Virus detection useful for case-management but negative

results can not exclude presence of SARS virus

– Ab detection comes too late in the course of the disease

• Negative test can not yet rule out earlier presence of

disease

Fonte:K. Stohr. WHO

Page 41: Pneumonia 1

SARS Síndroma respiratória aguda

• Não é o primeiro caso de SARS, nem será o último

• Legionelose 1976

• Hantanvírus 1993 EUA

• Hendra vírus 1994

• H5 N1 influenza vírus 1997

Hong Kong

• Nipah vírus 1997

• Metapneumovírus 2001

• H7 N7 influenza vírus 2003

Page 42: Pneumonia 1

SARS Síndroma respiratória aguda

• 50- 100 novos casos/DIA

• Definição de caso suspeito

caso provável

T > 38 º C

Tosse

Polipneia

Dispneia

Hipoxémia

Alt. Rx

eViagem ultimos 10 D início sintomas área SARS

China, Hong Kong, Formosa, singapura, Toronto, Vietnam

Contacto

com pessoa sint resp. E viagem região SARS

Com pessoa com SARS

Critérios clínicos

Critérios epidemiológicos

Critérios laboratoriais

- Acs SARS-CoV

- RT- PCR

- isolamento SARS- CoV

Page 43: Pneumonia 1

Fonte:CDC 16 MAIO

Preliminary Clinical Description of Severe Acute Respiratory Syndrome

Severe Acute Respiratory Syndrome (SARS) is a disease of unknown etiology that has been described in patients in Asia, North America, and Europe. Most patients identified as of March 21, 2003 have been previously healthy adults aged 25-70 years. A few suspected cases of SARS have been reported among children (≤15 years).

The incubation period of SARS is usually 2-7 days but may be as long as 10 days. The illness generally begins with a prodrome of fever (>38°C), which is often high, sometimes associated with chills and rigors and sometimes accompanied by other symptoms including headache, malaise, and myalgias.

At the onset of illness, some cases have mild respiratory symptoms. Typically, rash and neurologic or gastrointestinal findings are absent, although a few patients have reported diarrhoea during the febrile prodrome.

Page 44: Pneumonia 1

After 3-7 days, a lower respiratory phase begins with the onset of a dry, non-productive cough or dyspnea that may be accompanied by or progress to hypoxemia.

In 10%-20% of cases, the respiratory illness is severe enough to require intubation and mechanical ventilation.

The case fatality among persons with illness meeting the current WHO case definition for probable and suspected cases of SARS is around 3%.

Chest radiographs may be normal during the febrile prodrome and throughout the course of illness. However, in a substantial proportion of patients, the respiratory phase is characterized by early focal infiltrates progressing to more generalized, patchy, interstitial infiltrates. Some chest radiographs from patients in the late stages of SARS have also shown areas of consolidation.

Preliminary Clinical Description of Severe Acute Respiratory Syndrome

Fonte:CDC 16 MAIO

Page 45: Pneumonia 1

Preliminary Clinical Description of Severe Acute Respiratory Syndrome

Early in the course of disease, the absolute lymphocyte count is often decreased.

Overall white cell counts have generally been normal or decreased. At the peak of the respiratory illness, up to half of patients have leukopenia and thrombocytopenia or low-normal platelet counts (50,000 – 150,000 / μl).

Early in the respiratory phase, elevated creatine phosphokinase levels (up to 3000 IU / L) and hepatic transaminases (2- to 6-times the upper limits of normal) have been noted.

Renal function has remained normal in the majority of patients.

Fonte:CDC 16 MAIO

Page 46: Pneumonia 1

Preliminary Clinical Description of Severe Acute Respiratory Syndrome

Treatment regimens have included a variety of antibiotics to presumptively treat known bacterial agents of atypical pneumonia.

In several locations, therapy has also included antiviral agents such as oseltamivir or ribavirin.

Steroids have also been given orally or intravenously to patients in combination with ribavirin and other antimicrobials.

At present, the most efficacious treatment regime, if any is unknown.

Fonte:CDC 16 MAIO

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First data on stability and resistance of SARS coronavirus compiled by members of WHO laboratory network

The below table provides the first compilation of data on resistance of the SARS Coronavirus against environmental factors and disinfectants. WHO multi-center collaborative network on SARS diagnosis

The major conclusions from these studies are:

Virus survival in stool and urine

• Virus is stable in faeces(and urine) at room temperature for at least 1-2 days.

• Virus is more stable (up to 4 days) in stool from diarrhea patients (which has higher pH than normal stool).

Fonte:CDC 16 MAIO

Page 48: Pneumonia 1

• Disinfectants

•Virus loses infectivity after exposure to different commonly used disinfectants and fixatives.

• Virus survival in cell-culture supernatant

• Only minimal reduction in virus concentration after 21 days at 4°C and -80°C.

• Reduction in virus concentration by one log only at stable room temperature for 2 days. This would indicate that the virus is more stable than the known human coronaviruses under these conditions. • Heat at 56°C kills the SARS coronavirus at around 10000 units per 15 min (quick reduction).

• Fixatives (for use in laboratories only)

• SARS virus fixation (killing) on glass slides for immunofluorescence assays in room temperature does not kill virus efficiently unless the acetone is cooled down to -20oC.

Fonte:CDC 16 MAIO

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Worldwide 6727 cases 478 deaths

Europe 36 cases 0 deaths

0.5% of totalFonte: OMS

SARS- 6 MAIO

Page 50: Pneumonia 1

Total countries 29

Europe 11

Fonte: OMS

SARS- 6 MAIO

Page 51: Pneumonia 1

Fonte: OMS

SARS- 6 MAIO

Italy 9Germany 7UK 6 France 5Sweden 3 Bulgaria 1Poland 1Rep of Ireland 1Romania 1Spain 1Switzerland 1

Page 52: Pneumonia 1

Worldwide 6727 cases 478 deaths

Europe 36 cases 0 deaths

0.5% of total

Fonte: OMS

SARS- 6 MAIO

SARS- 16 MAIO

Worldwide 7739 cases 611 deaths

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SARS Síndroma respiratória aguda

• este caso é importante para lembrar

constante ameaça das D. Infecciosas

possibilidade de aparecimento novos agentes infecciosos

Page 55: Pneumonia 1

Apesar dos avanços terapêuticos

“ Os esforços para controlar as infecções respiratórias não

podem ser estáticos, dada a emergência de novos

patogéneos e o aparecimento de resistências aos

antibióticos comuns nos patogéneos antigos”

Michael Niederman

Novos Fármacos