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Year 2 - BRS > 5.13 - Respiratory tract infections and immunity > Flashcards

5.13 - Respiratory tract infections and immunity Flashcards

1
Q

What are the symptoms of upper respiratory tract infections? (5)

A
  • cough
  • sneezing
  • runny/stuffy nose
  • sore throat
  • headache
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2
Q

What are the symptoms of lower respiratory tract infections? (6)

A
  • ‘productive’ cough - phlegm
  • muscle aches
  • wheezing
  • breathlessness
  • fever
  • fatigue
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3
Q

What are the symptoms of pneumonia? (4)

A
  • chest pain
  • blue tinting of lips
  • severe fatigue
  • high fever
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4
Q

What is the frequency and severity of upper RTI, lower RTI and pneumonia?

A

Increasing severity, decreasing frequency

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5
Q

What does it mean that respiratory infections often display progressive symptomology?

A

We can go from upper respiratory tract symptoms to lower respiratory tract symptoms over time

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6
Q

How many deaths do acute respiratory infections cause?

A
  • respiratory infection resulted in ~5 million deaths annually between 1990 and 2015
  • about 3 million deaths annually from acute lower respiratory infections
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7
Q

How many people are estimated to have latent TB?

A

Estimated that 1 in 4 people have latent TB, 1.4 million deaths from TB in 2019

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8
Q

What are DALYs?

A

Disability-adjusted life year: sum of Years of Life Lost (YLL) + Years Lost to Disability (YLP)

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9
Q

Why are acute lung infections the leading cause of global DALYs lost but not global deaths?

A
  • the fact that you can survive an acute infection often, but have persistent changes in respiratory tract that is disabling
  • partly due to age groups affected
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10
Q

What ages does most mortality happen for respiratory infections?

A
  • adults older than 70
  • children under 5
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11
Q

How big a cause of death are respiratory infections in infants?

A
  • leading cause of death <1y, and second leading cause of death between 1-5y
  • a mix of viral and bacterial causes of respiratory illness (RSV is main one)
  • pneumonia and bronchiolitis present
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12
Q

What are demographic and lifestyle risk factors for pneumonia? (3)

A
  • age <2y / >65y
  • cigarette smoking
  • excess alcohol consumption
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13
Q

What are social risk factors for pneumonia? (3)

A
  • contact with children aged <15y
  • poverty
  • overcrowding
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14
Q

What are medication risk factors for pneumonia? (3)

A
  • inhaled corticosteroids
  • immunosuppressants (e.g. steroids)
  • proton pump inhibitors
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15
Q

What medical conditions are risk factors for pneumonia? (8)

A
  • COPD, asthma
  • heart disease
  • liver disease
  • diabetes mellitus
  • HIV, malignancy, hyposplenism
  • complement or Ig deficiencies
  • risk factors for aspiration
  • previous pneumonia
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16
Q

What are specific risk factors for certain pathogens causing pneumonia? (3)

A
  • geographical variations
  • animal contact
  • healthcare contacts
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17
Q

What are the main bacterial causative agents of respiratory infections? (4)

A
  • Streptococcus pneumoniae
  • Mycoplasma pneumoniae
  • Haemophilus influenzae
  • Mycobacterium tuberculosis
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18
Q

What are the main viral causative agents of respiratory infections? (5)

A
  • influenza A/B
  • respiratory syncytial virus (RSV)
  • human metapneumovirus
  • human rhinovirus
  • coronaviruses
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19
Q

What are the bacterial causes of community acquired pneumonia (CAP)? (5)

A
  • Streptococcus pneumoniae (40-50%)
  • Mycoplasma pneumoniae
  • Staphylococcus aureus
  • Chlamydia pneumoniae
  • Haemophilus influenzae
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20
Q

What are the bacterial causes of hospital acquired pneumonia? (6)

A
  • Staphylococcus aureus
  • Pseudomonas aeruginosa
  • Klebsiella species
  • E. coli
  • Acinetobacter spp.
  • Enterobacter spp.
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21
Q

What is the main thing you need to remember about the bacterial causes of community acquired pneumonia and hospital acquired pneumonia?

A
  • CAP –> Streptococcus pneumoniae
  • HAP –> Staphylococcus
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22
Q

What are the bacterial causes of ventilator associated pneumonia? (3)

A
  • Pseudomonas aeruginosa (25%)
  • Staphylococcus aureus (20%)
  • Enterobacter
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23
Q

What is Streptococcus pneumoniae?

A

Gram-positive, extracellular, opportunistic pathogen

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24
Q

What is typical pneumonia?

A
  • most common type
  • caused by most common forms of bacteria (e.g. Streptococcus pneumoniae)
  • rapid, fever, breathlessness, confusion
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25
Q

What is atypical pneumonia?

A
  • less frequent
  • distinct bacterial species e.g. M. pneumoniae is a simple gram-negative bacteria
  • slower onset of symptoms and milder
  • ‘walking pneumonia’
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26
Q

What are examples of bacteria that cause typical pneumonia? (3)

A
  • Streptococcus pneumoniae
  • Haemophilus influenzae
  • Moraxella catarrhalis
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27
Q

What are examples of bacteria that cause atypical pneumonia? (3)

A
  • Mycoplasma pneumoniae
  • Chlamydia pneumoniae
  • Legionella pneumophilia
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28
Q

What are the features present in acute bacterial pneumonia?

A
  • bronchitis - inflammation and swelling of bronchi
  • bronchiolitis - inflammation and swelling of bronchioles
  • pneumonia - inflammation and swelling of alveoli
  • these stop gas exchange occurring
  • inflammation independent of bacteria (sometimes bacteria cleared but inflammation continues)
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29
Q

What are the two routes of damage in pneumonia?

A
  • sepsis - organ infection from bacteraemia (caused by spread throughout the body)
  • ARDS - acute respiratory distress syndrome by lung damage (caused by the physiological damage of the alveoli by the bacteria)
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30
Q

What are the mechanisms of damage in pneumonia?

A
  • lung injury –> arterial hypoxemia –> ARDS
  • bacteraemia –> organ infection + systemic inflammation + lung injury/arterial hypoxemia –> organ injury or dysfunction –> sepsis + deterioration (decrements in pulmonary, cardiovascular, neuromuscular, haematologic, cognitive, psychologic and other functions)
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31
Q

What is the difference in the lung biopsy of pneumonia compared to normal?

A

Can see cells and fluid infiltrate

32
Q

How do we grade potential bacterial pneumonia?

A

CRB/CURB-65 scoring (1 point per item)

  • Confusion
  • Urea: > 7mmol/L (add if in hospital)
  • Respiratory rate: >30 breaths/min
  • Blood pressure: <90 systolic and/or <60 mmHg diastolic
  • 65 years or older
33
Q

How do you treat patients with different CRB65 scores?

A
  • 0: low severity - likely suitable for home treatment, antibiotics
  • 1-2: moderate severity - consider hospital referral
  • 3-4: high severity - urgent hospital admission, empirical antibiotics if life-threatening
  • consider social circumstances and home support when deciding on whether to refer to hospital or manage in community

Urea not included since initial score may not be in hospital setting, can consider CURB-65 3-5 as high severity

34
Q

What supportive therapy is there for bacterial pneumonia? (5)

A
  • oxygen (for hypoxia)
  • fluids (for dehydration)
  • analgesia (for pain)
  • nebulised saline (may help expectoration - coughing up mucus)
  • chest physiotherapy?
35
Q

What antibiotics are there for bacterial pneumonia? (2 types)

A
  • penicillins e.g. amoxicillin - beta lactams that bind proteins in the bacterial cell wall to prevent transpeptidation (typical pneumonia)
  • macrolides e.g. clarithromycin - bind to the bacterial ribosome to prevent protein synthesis (atypical pneumonia)
36
Q

What is the key to increasing the success of antibiotics in pneumonia?

A
  • the time to administration (for every hour in septic shock, survival is reduced by 7.9%)
  • using an effective antibiotic - typical CAPs may respond to penicillins, atypical CAPs require macrolides
37
Q

Can you catch pneumonia and why?

A

No, because a lot of the time the bacteria that cause it are commensal and part of the microbiome

38
Q

What is the human microbiome?

A

100 trillion microbial cells populate our bodies at every barrier surface

39
Q

What is the microbiota?

A

Ecological communities of microbes found inside multi-cellular organisms

40
Q

What does commensal mean?

A
  • microbes that live in a ‘symbiotic’ relationship with their host
  • provide vital nutrients to the host in the presence of a suitable ecological niche
41
Q

What are examples of commensal bacteria in the oropharynx?

A
  • STREPTOCOCCUS PNEUMONIAE
  • STAPHYLOCOCCUS AUREUS
  • HAEMOPHILUS SPP.
  • strep. viridans
  • coagulase neg. staph
  • veronella
  • fusiforms
  • treponena spp.
  • beta-haem strep
42
Q

What are examples of commensal bacteria in the nose?

A
  • STREPTOCOCCUS PNEUMONIAE
  • STAPHYLOCOCCUS AUREUS
  • coagulase neg. staph
  • haemophilus spp.
  • strep. viridans
43
Q

What is an opportunistic pathogen?

A

A microbe that takes advantage of a change in conditions (often immunosuppression)

44
Q

What is a pathobiont?

A

A microbe that is normally commensal, but if found in the wrong environment (e.g. anatomical site) can cause pathology

45
Q

What do opacities on a lung X-ray mean?

A

Fluid build-up due to bacterial or viral pneumonia

46
Q

What do viral diseases do to cause disease?

A
  • mediator release
  • cellular inflammation
  • local immune memory
  • damage to epithelium:
    • loss of cilia
    • bacterial growth
    • poor barrier to antigen
    • loss of chemoreceptors
47
Q

Why do viruses cause severe disease - RTIs? (3)

A
  • highly pathogenic strains (zoonotic - spread between animals and people)
  • absence of prior immunity (innate immunodeficiency e.g. IFITM3 gene variant, B cells, T cells)
  • predisposing illness/conditions e.g. frail elderly, COPD/asthma, diabetes, obesity, pregnancy etc
48
Q

What is it important to know about virus binding?

A

Most respiratory viruses can infect cells throughout the respiratory tract, but tend to preferably adapt to bind cells of the upper respiratory tract if they have existed in humans for a prolonged time

49
Q

Where does H1N1 influenza A bind?

A

Haemagglutinin on H1N1 binds alpha-2,6 sialic acids on epithelial cells in upper respiratory tract (nose, pharynx)

50
Q

Where does H5N1 avian flu bind?

A

Haemagglutinin on H5N1 binds alpha-2,3 sialic acids on epithelial cells in lower respiratory tract (nasopharynx)

51
Q

How does the respiratory epithelium act as first line of defence against pathogens? (5)

A
  • tight junctions
  • mucous lining and cilial clearance
  • antimicrobials
  • pathogen recognition receptors
  • interferon pathways
52
Q

Where does SARS-Cov-2 bind?

A
  • spike (S) protein binds angiotensin converting enzyme 2 (ACE2)
  • ACE2 is expressed highly in nasal epithelium and in type 2 pneumocytes in lungs (higher in smokers) –> nasal symptoms e.g. anosmia + high risk of pneumonia
53
Q

What do tight junctions do (respiratory epithelium as first line of defence)?

A

Prevents systemic infection

54
Q

What does mucous lining and cilial clearance do (respiratory epithelium as first line of defence)?

A

Prevents attachment, clears particulates

55
Q

What do antimicrobials do (respiratory epithelium as first line of defence)?

A

Recognise, neutralise and/or degrade microbes and their products

56
Q

What do pathogen recognition receptors do (respiratory epithelium as first line of defence)?

A

Recognise pathogens either outside or inside a cell

57
Q

What do interferon pathways do (respiratory epithelium as first line of defence)?

A
  • activated by viral infection
  • promotes upregulation of antiviral proteins and apoptosis
58
Q

What is a serotype?

A

Pathogens which cannot be recognised by serum (antibodies) that recognise another pathogen - implications for protective immunity, need to mount a unique antibody response

59
Q

What is an antigen?

A

Any molecule against which antibodies can be generated

60
Q

What is antibody mediated immunity?

A
  • humoral immunity
  • adaptive, so dependent on previous exposure
  • B cells activated to differentiate into antibody-secreting plasma cells
  • different antibody classes provide different biochemical properties and functions
61
Q

What kind of antibody is common in the upper respiratory tract?

A
  • enriched for IgA
  • high frequency of IgA-plasma cells
  • endothelial cells express poly IgA receptor, allowing export of IgA to the mucosal surface
  • homodimer is extremely stable in protease-rich environment
62
Q

What kind of antibody is common in the lower respiratory tract?

A
  • enriched for IgG
  • thin-walled alveolar space allows transfer of plasma IgGs into the alveolar space
63
Q

What is the potential issue with too much IgG?

A

Too much inflammation and damage in exchange surfaces

64
Q

Compare influenza, RSV and SARS-CoV-2 in terms of immunity.

A
  • influenza: no reinfection by same strain
  • RSV: recurrent reinfection with similar strains
  • SARS-CoV-2: no prior immunity
65
Q

Compare influenza, RSV and SARS-CoV-2 in terms of vaccines.

A
  • influenza: imperfect vaccines - vaccine-induced immunity rapidly wanes, mainly homotypic immunity and annual vaccination required
  • RSV: no vaccine - poor immunogenicity, vaccine-enhanced disease, very active research field
  • SARS-CoV-2: newly licensed vaccine - waning immunity, potential for reinfection, unclear what regime will be required
66
Q

What are some epidemiological facts about RSV (respiratory syncytial virus) in children?

A
  • leading cause of infant hospitalisation in the developed world
  • 50% of children infected in year 1 of life, all children by year 3
  • 1% develop severe bronchiolitis
  • can repeatedly infect children
  • similar viruses at lower prevalence include hMPV and PIV
67
Q

What are the symptoms of RSV in infants? (6)

A
  • nasal flaring
  • croupy cough
  • chest wall retractions
  • hypoxaemia and cyanosis
  • tachypnoea with apnoeic episodes
  • expiratory wheezing, prolonged expiration, rales and rhonchi
68
Q

What are the risk factors for RSV in infants? (2)

A
  • premature birth
  • congenital heart and lung disease
69
Q

How do we treat RSV in infants?

A

Give oxygen - usually helps

70
Q

What supportive therapy do we give for viral infections? (5)

A
  • oxygen (for hypoxia)
  • fluids (for dehydration)
  • analgesia (for pain)
  • nebulised saline (may help expectoration)
  • chest physiotherapy?
71
Q

What preventative/prophylactic measures are there for viral infections? (3)

A

Vaccines:

  • major surface antigen - spike protein
  • viral vector (e.g. adenovirus vaccine Oxford/AZ)
  • mRNA vaccines (e.g. BioNtech/Pfizer)
72
Q

What anti-inflammatory therapeutic medications can be given for viral infection? (2)

A
  • dexamethasone (steroids)
  • tocilizumab (anti-IL6R) or sarilumab (anti-IL6)
73
Q

What anti-virals are there for viral infection? (3)

A
  • remdesivir - broad spectrum antiviral, blocks RNA-dependent RNA polymerase activity
  • paxlovid - antiviral protease inhibitor
  • casirivimab and imdevimab - monoclonal neutralising antibodies for SARS-CoV-2
74
Q

What do viruses set the scene for?

A
  • for bacterial infections, especially bacterial pneumonia
  • 55% of rhinovirus-infected COPD patients also have bacterial infections
75
Q

How do viruses interplay with other lung diseases? (3)

A
  • viral bronchiolitis is associated with the development of asthma
  • rhinoviruses are the most common cause of asthma/COPD exacerbations
  • high likelihood of secondary bacterial pneumonia after viral infection
76
Q

What does age dependence mean in terms of RSV?

A
  • children - infantile bronchiolitis, causally related to wheeze, older siblings spreaders
  • caring adults - repeated colds, transmitters, rarely severe
  • old and infirm - major cause of progressive lung disease and winter deaths
77
Q

If an infant presents with a viral infection, what is the most likely cause?

A

RSV

Year 2 - BRS (84 decks)

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