respiratory tract infection

Question 1

potential evolution line of a resp tract infection?

Answer 1

upper respiratory tract infection (cough sneezing runny nose sore throat and headache) → lower resp tract infection (a productive cough muscle aches wheezing breathlessness fever and fatigue) → pneumonia (chest pain blue tinging of lips severe fatigue and high fever)

Question 2

which is worse - upper or lower tract infections?

Answer 2

lower → among the leading causes of death in the world

Question 3

what factor has a significant effect on mortality burden?

Answer 3

age

Question 4

risk factors for pneumonia?

Answer 4

• demographic/lifestyleage under 2 or 65+cigarette smoking, excess alcohol
• social factorsclose contact with children <15 and overcrowding, poverty
• medicationsinhaled corticosteroidsimmunosuppressantsPPIs
• medical historyCOPD, asthma, DM, heart/liver diseaseHIV, malignancy, hyposplenismcomplement/Ig deficienciesaspiration risk factorsprevious pneumonia

geographical variation,animal contect,healthcare contact

Question 5

common causative agents for resp infections?

Answer 5

• bacterialstreptococcus pneumoniaemycoplasma pneumoniaehaemophilus influenzaemycobacterium tuberculosis
• viralinfluenza A/Brespiratory syncytial virushuman metapneumovirusrhinoviruscorona viruses

Question 6

differences in common causative agents in CAP and HAP?

Answer 6

community acquired → strep pneumoniae, mycoplasma pneumoniae,haemophilus influenza,staph.aureus,chlamydia pneumonia
say my surname child

hospital acquired → staph aureus, pseudomonas aeruginosa,klebsiella species,E coli,acinetobacter spp,enterobacter spp
she pretends kids eat all eggs

ventilator acquired–>
pseudomonas areuginosa
staphylococcus aureus
enterobacter

Question 7

subtypes of acquired pneumonia?

Answer 7

typical vs atypical
typical → common bacterial species eg streptococcus pneumonia,haemophillus influenza and moraxella catarrhalis. SMH

atypical → more distinct species, slower onset of symptoms, milder eg mycoplasma pneumonia,chlamydia pneumonia,legionella pneumophilia MLC. also have walking pneumonia .They are more difficult to culture so might need a different abx regime

Question 8

what is the difference in treatment? pneumoonia subtypes

Answer 8

typical = often penicillin eg amoxicilin beta lactams that bind protein in the bacterial cell wall to prevent transpeptidation

atypical = often penicillin + macrolides eg clarithromycin bind to bacterial ribosomes to prevent protein synthesis

Question 9

how is potential bacterial pneumonia graded?

Answer 9

use CRB-65 / CURB-65 scoring

1 point for each of:

confusion, resp rate > 30, blood pressure under 90 syst and/or 60 dias, 65 yo or older

in hospital: urea over 7 mmol/L

Question 10

CURB-65 scoring boundaries

Answer 10

0 = low severity, 1-2 = moderate severity (consider hospital), 3-4 = high severity (urgent hospital, empirical antibiotics if life threatening)

Question 11

bacterial pneumonia treatment?

Answer 11

supportive therapy → oxygen, fluids, analgesia,neubulised saline and chest physio?

antibiotics → penicillins, macrolides

Question 12

what is an opportunistic pathogen?

Answer 12

microbe that takes advantage of a change in conditions e.g. immunosuppression to cause infection

Question 13

what is a pathobiont?

Answer 13

microbe that is normally commensal but can cause illness if found in the wrong place

Question 14

factors that can cause variable disease outcomes?

Answer 14

specific strains of causative agent, absence/presence of prior host immunity, predisposing illnesses and conditions

Question 15

where in the respiratory tract do viruses tend to infect?

Answer 15

if virus has existed in humans for a long time → adapt to preferentially target cells in upper resp tract

Question 16

defence mechanisms of the respiratory epithelium?

Answer 16

tight junctions

mucous lining and cilial clearance

antimicrobials, pathogen recognition receptors, interferon pathways

Question 17

what are serotypes?

Answer 17

different serotypes = can’t be recognised by same serum/antibody

Question 18

antibody distribution in respiratory tract?

Answer 18

upper → high frequency of IgA plasma cells. Dimeric not inflammatory and protease resistant

lower → enriched for IgG - thin alveolar walls allows transfer of plasma IgG into alveolar space. Smaller ,Covid vaccine generated large amounts of this tor deuce severity

Question 19

what is RSV?

Answer 19

respiratory syncytial virus

Question 20

characteristics of infection?

Answer 20

repeated infection by similar strains possible

Question 21

in what subset of the population is it particularly prevalent?

Answer 21

babies → almost all children have had it by age 3

Question 22

what does RSV cause

Answer 22

1% - severe bronchiolitis

croupy cough, hypoxemia and cyanosis, expiratory wheeze, tachypnea with apneic episodes, chest wall retraction

Question 23

risk factors of rsv

Answer 23

premature birth, congenital heart and lung disease

Question 24

SARS-CoV-2 treatment options?

Answer 24

supportive → oxygen, fluids, analgesia

prophylactic → vaccine

therapeutic → anti-inflammatory e.g. dexamethasone

antivirals → remdesivir broad spectrum, monoclonal antibodies possible, paxlovid an antiviral protease inhibitor,casirivimab and imdevimab (monoclonal antibodies)

Question 25

features of interplay between bacterial, viral and chronic lung diseases?

Answer 25

viral bronchiolitis → asthma development association rhinoviruses (and other transient infections) can cause exacerbations of chronic disease like COPD, asthma high likelihood of secondary bacterial pneumonia after viral resp infection

Question 26

ventilator associated pneumonia

Answer 26

pseudomonas aeruginosa staphylococcus aureus enterobacter

Question 27

why do viral infections cause disease

Answer 27

epithelial damage leads to loss of cilia,reduced barrier integrity,bacterial growth leads to airway narrowing fluid and mucus build up in airways and parenchyma damage to gas exchange surfaces

Question 28

serotypes

Answer 28

viruses which cant be recognised by serum that recognise another virus-implications for protective immunity

Question 29

IFN-I

Answer 29

important role in viral infection inhibits viral replicstion and activates antiviral state

Question 30

innate immunity

Answer 30

alveolar macrophages-phagocytosis,tissue homeostasis and pathogen sensing resident dendritic cells-respond to inflammation and take up and present foreign antigen driving adaptive immune response neutrophils-main cell type recrutied upon infection,can cause inflammatory damage NK cells-provide innate antiviral immunity against infected cells monocytes-resukts into site to provide mediators and macrophage sources

Question 31

antibody mediated immunity

Answer 31

humoral immunity adaptive so dependant on prior exposure b cells activated to differentiate into antibody secreting plasma cells different antibody classes provide different biochemical properties and function

Question 32

Where do influenza bird flu rhinovrius and Covid bind

Answer 32

Influenza A:haemagluttinin binds to alpha 2,6 sialic acid Bird flu (H5N1 avian flu): haemaglutinin binds to alpha 2,3 sialic acid (common in lower resp tract) Covid:spike proteins bind to ACE2 high in pneumocytes and nasal epithelium and increased expression in smokers common cold rhinoviruses: bind to ICAM-1 (major group) and LDLR (minor group)

Question 33

Treatment for CAP with respect to CURB-65

Answer 33

Treat the patient for 5-7 days for typical pneumonia, and 7-14 days for atypical - 0 ⇒ Amoxicillin (or clarithromycin / doxycycline if allergic to penicillin) - 1-2 ⇒ Amoxicillin AND clarithromycin (replace amoxicillin with doxycycline if allergic) - 3-5 ⇒ Benzylpenicillin IV with oral clarithromycin (replace benzyl with teicoplanin if allergic)

Question 34

Treatment for HAP with respect to CURBx 65

Answer 34

Treat for 5-7 days 0 ⇒ NOT severe so treat with oral doxycycline 1-2 ⇒ NOT severe so treat with oral doxycycline 3-5 ⇒ SEVERE so treat with tazocin (piperacillin-tazobactam) IV, with or without gentamicin IV

Question 35

asthma as a riskfactor for pneumonia

Answer 35

Exacerbations are the most common cause of hospitalisation resp infections specifically viral are the major cause of exacerbations Hospitalisations due to exacerbations are the major predictor of asthma mortality severe exacerbations are less common

Question 36

how does acute bacterial pneumonia cause damage

Answer 36

bronchilitis which is inflammation and swelling of bronchi bronchiolitis which is inflammation and swelling of the bronchioles pneuomnia which is inflammtion and swelling of the alveoli

Question 37

pneuomnia mechanism of action

Answer 37

lung injury causes arterial hypoxemia which leads to ARDS or organ injury and dysfunction causing sepsis or deterioration bacteremia causes organ infection which causes organ injury or dysfunction leading to sepsis or deterioration systemic inflammation causes organ dysfunction leading to sepsis or deterioration treatment can also lead to deterioration

Question 38

commensal bacteria and pneumonia

Answer 38

oropharynx contains haemophillus,staph aureus and strep pneumonia nose contains staph aureus and strep pneuomnia These commensal bacteria can become opportunistic and cause pneumonia if your immune system weakness,hospitalisation and viral infections

Question 39

physical and chemical barriers of the resp epithelium

Answer 39

Tight junctions – prevents systemic infection Mucous lining and cilial clearance – prevents attachment, clears particulates Antimicrobials – recognise, neutralise and/or degrade microbes and their products Pathogen recognition receptors – recognise pathogens either outside or inside a cell Interferon pathways – activated by viral infection. Promotes upregulation of anti-viral proteins and apoptosis.

Question 40

antibodies present

Answer 40

Enriched for IgA High frequency of IgA-plasma cells ECs express poly IgA receptor, allowing export of IgA to the mucosal surface Homodimer is extremely stable in protease rich environment Enriched for IgGs Thin-walled alveolar space allows transfer of plasma IgGs into the alveolar space

Question 41

serotypes of rhinovirus influenza rsv and sars cov2

Answer 41

rhinovirus 100-300+ different serotypes within RV-A, B and C strains. Long lasting antibody mediated immunity. influenxa No re-infection by same strain Influenza strains ”drift” and ”shift” surface antigens (HA, N) to avoid antibody mediated immunity rsv Recurrent infection with the same serotype/strain. Limited mutation of surface antigens. (F, G). Natural antibodies wane rapidly allowing re-infection. sars cov2 Antigenically novel coronavirus. No prior exposure. Antibodies wane over time. Some evidence of surface antigen mutation

Question 42

treatment for sars cov2

Answer 42

supportive therapy oxygen,fluids,analgesia,nebulied saline,chest physio? preventative/prophylatic vaccines,major surafce antigen (spike protein),viral vector eg adenovirus vaccine or mrna vaccines therapeutic anti inflammatory eg dexamethasone (steroid) and tocolizumab (anti IL6R) or sarilumab (anti il6) anti virals remdesivir which is a broad spec antivrial and blocks rna dependant rna polymerase activity paxlovid which is an antiviral protease inhibitor casirivimab and imdevimab which is a monoclonal neutralising antibody for sars cov 2

Question 43

interplay of viral infections with chronic lung disease

Answer 43

viral bronchiolitis is associated with the development of astma rhinovrius is the most common cause of asthma and copd high likelihood of secondary bacterial pneumonia after viral infecion

Question 44

Strep pneumonia

Answer 44

Gram positive Extracellular opportunistic pattern