PATOLOGIA DO APARELHO RESPIRATÓRIO
Carlos Robalo Cordeiro
Pneumonias
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
Pneumonia
Hospitalar
sintomas e sinais de Infecção.R.aguda
+
alterações radiológicas
In THORAX 2001, 56, (suppl4)- BTS GUIDELINES 2001
Classificação
radiológica
segmentareslobaresintersticiais
broncopneumonia histológica
alveolaresintersticiais
etiológicabacterianavirusalfúngica
tipo de evoluçãoagudassubagudascrónicas
Classificação
epidemiológica
PACPN/PHP.
Imunodeprimido
Epidemiologia
Maioria tratada em ambulatório
0- 42 % requerem hospitalização
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
• 30- 60 % impossível identificar
• agente etiológico varia consoante:
- área geográfica
- idade
- patologias associadas
DPOC
Patologia CV
DM
Lar
Alcoolismo
CT
Etiologia
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
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
• 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
• clínica
• exame objectivo
• radiologia
confirmação DX
localização
extensão
complicações
Diagnóstico
• radiologia
p. alveolar
p. broncopneumónico
p. intersticial
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
Consolidação do lobo inferior direito
• Exmes laboratoriais
Exame directo
Cultura
Hemograma
Bioquímica
GSA
Hemoculturas
Serologia VIH
Serologias específicas
Diagnóstico
Pneumonia Típica // Atípica ???
- Apresentação clínico-radiológica diferente ?
- sobreposição de achados ?
- AB b- lactâmicos ineficazes
- meios de diagnóstico específicos
- terapêutica diferente
Pneumonia Atípica
- etiologia:
Mycoplasma pneumoniae
Chlamydia pneumoniae
Chlamydia psitacci
Legionella pneumophila
Coxiella burnetti
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
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
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
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
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
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
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
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
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
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
SARS Síndroma respiratória aguda
Alerta global
• Casos iniciais:
China
Vietnam
Indonésia
Filipinas
Singapura
• descohecimento do agente etiológico
• mortalidade
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
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
Severe Acute Respiratory Syndrome (SARS): Global Alert, Global Response
World Health Organization
K. Stohr
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
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
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
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
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
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.
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
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
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
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
• 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
Worldwide 6727 cases 478 deaths
Europe 36 cases 0 deaths
0.5% of totalFonte: OMS
SARS- 6 MAIO
Total countries 29
Europe 11
Fonte: OMS
SARS- 6 MAIO
Fonte: OMS
SARS- 6 MAIO
Italy 9Germany 7UK 6 France 5Sweden 3 Bulgaria 1Poland 1Rep of Ireland 1Romania 1Spain 1Switzerland 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
SARS Síndroma respiratória aguda
• este caso é importante para lembrar
constante ameaça das D. Infecciosas
possibilidade de aparecimento novos agentes infecciosos
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