Respiratory Tract Infections & Immunity Flashcards by Notis Tzionis

Outline the epidemiology of respiratory infections (Deaths / Age 3).

Deaths:
* Estimated 5 million deaths annually between 1990 - 2015
* About 3 million deaths annually from acute lower respiratory infections

Age:
* Age dramatically impacts mortality burden
* Over 70
* Under 5
* Pneumonia rates increase with age

Mortality burden definition:
* DALY – Disability-adjusted Life Year: A sum of Years of Life Lost (YLL) and Years Lost to Disability (YLP)

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What are the risk factors of respiratory infections (pneumonia) divided into (5)?

Demographic and lifestyle factors:
* Age < 2 years or > 65 years
* Cigarette smoking
* Excess alcohol consumption

Social factors:
* Contact with children aged < 15 years
* Poverty
* Overcrowding

Medications:
* Inhaled corticosteroids
* Immunosuppresants (e.g steroids)
* Proton pump inhibitors

Medical history:
* COPD
* Asthma
* Heart disease
* Liver disease
* Diabetes mellitus
* HIV
* Malignancy
* Hyposplenism
* Complement or Ig deficiencies
* Risk factors for aspiration
* Previous pneumonia

Specific risk factors for certain pathogens:
* Geographical variations
* Animal contact
* Healthcare contacts

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What are the demographic and lifestyle risk factors of respiratory infections (pneumonia) (3)?

Demographic and lifestyle factors:
* Age < 2 years or > 65 years
* Cigarette smoking
* Excess alcohol consumption

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What are the social risk factors of respiratory infections (pneumonia) (3)?

Social factors:
* Contact with children aged < 15 years
* Poverty
* Overcrowding

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What are the medication risk factors of respiratory infections (pneumonia) (3)?

Medications:
* Inhaled corticosteroids
* Immunosuppresants (e.g steroids)
* Proton pump inhibitors (PPIs)

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What are the medical history risk factors of respiratory infections (pneumonia) (11 / know 5)?

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What are the specific risk factors for certain pathogens of respiratory infections (pneumonia) (3)?

Specific risk factors for certain pathogens:
* Geographical variations
* Animal contact
* Healthcare contacts

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Outline the pathogenesis of respiratory infections (2).

Through (common) causative agents:

Bacterial:
* Streptococcus pneumoniae
* Myxoplasma pneumoniae
* Haemophilus Influenzae
* Mycobacterium tuberculosis

Viral:
* Influenza A or B virus
* Respiratory Syncytial Virus
* Human metapneumovirus
* Human rhinovirus
* Coronaviruses

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What are the common bacterial causes of respiratory infections (4)?

Bacterial:
* Streptococcus pneumoniae
* Myxoplasma pneumoniae
* Haemophilus Influenzae
* Mycobacterium tuberculosis

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What are the common vacterial causes of respiratory infections (5)?

Viral:
* Influenza A or B virus
* Respiratory Syncytial Virus
* Human metapneumovirus
* Human rhinovirus
* Coronaviruses

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How would a patient with upper respiratory tract infection present (5)?

Cough
Sneezing
Runny or stuffy nose
Sore throat
Headache

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How would a patient with lower respiratory tract infection present (6)?

A “productive” cough - phlegm
Muscle aches
Wheezing
Breathlessness
Fever
Fatigue

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How would a patient with pneumonia present (4)?

Pneumonia is a medical condition that affects the lungs, characterized by inflammation of the air sacs in one or both lungs, which can be caused by a variety of infectious agents such as bacteria, viruses, or fungi.

Chest pain
Blue tinting of the lips
Severe fatigue
High fever

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What are the 3 different types of pneumonia?

Community acquired pneumonia (CAP)
Hospital acquired pneumonia (HAP)
- Ventilator associated pneumonia (VAP)

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

Streptococcus pneumoniae (40-50%)
Myxoplasma pneumoniae
Staphylococcus aureus
Chlamydia pneumoniae
Haemophilus Influenzae

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

Staphylococcus aureus
Psuedomonas aeruginosa
Klebsiella species
Escherichia coli (E. coli)
Acinetobacter spp.
Enterobacter spp.

What are the main bacterial causes of ventilator acquired pneumonia (VAP) (3)?

Psuedomonas aeruginosa (25%)
Staphylococcus aureus (20%)
Enterobacter

What are the most typical causes of pneumonia (3)?

Streptococcus pneumoniae
Haemophilus influenzae
Moraxella catarrhalis

What are the most atypical causes of pneumonia (3)?

Mycoplasma pneumoniae
Chlamydia pneumoniae
Legionella pneumophilia

Outline the pathophysiology of acute bacterial pneuonia.

What is CURB-65 scoring?

A grading potential bacterial pneumonia

Describe the CURB-65 scoring system.

Confusion
(In hospital add) Urea
- > 7 mmol/L
Respiratory rate
- > 30 breaths/min
Blood pressure
- < 90 systolic and / or 60 mmHg diastolic
65 years old or older

1 point per item

What is the management of bacterial pneumonia divided into (2)?

Supportive therapy
Treatments

What is the supportive therapy recommended for the management of bacterial pneumonia (5)?

Oxygen (for hypoxia)
Fluids (for dehydration)
Analgesia (for pain)
Nebulised saline (may help expectoration)
Chest physiotherapy

What is the treatment for the management of bacterial community accquired pneumonia (CAP) with CURB-65 score of 0 (1)?

**Penicillins** * Amoxicillin (or clarithromycin/ doxycycline if pen. allergic) ## Footnote Penicillins e.g. amoxicillin – beta lactams that bind proteins in the bacterial cell wall to prevent transpeptidation

What is the treatment for the management of bacterial hospital accquired pneumonia (HAP) with CURB-65 score of 0 (1)?

**Penicillins** * NOT SEVERE: doxycycline PO ## Footnote Penicillins e.g. amoxicillin – beta lactams that bind proteins in the bacterial cell wall to prevent transpeptidation

What is the treatment for the management of bacterial community accquired pneumonia (CAP) with CURB-65 score of 1-2 (2)?

**Penicillins + Macrolides** * Amoxicillin + clarithromycin (or clarithro./doxy.) ## Footnote Penicillins e.g. amoxicillin – beta lactams that bind proteins in the bacterial cell wall to prevent transpeptidation Macrolides e.g. clarithromycin – bind to the bacterial ribosome to prevent protein synthesis

What is the treatment for the management of bacterial community accquired pneumonia (CAP) with CURB-65 score of 3-4 (2)?

**Penicillins + Macrolides** * Benzyl-penicillin IV + clarithro. PO (or teicoplanin + clarithro.) ## Footnote Penicillins e.g. amoxicillin – beta lactams that bind proteins in the bacterial cell wall to prevent transpeptidation Macrolides e.g. clarithromycin – bind to the bacterial ribosome to prevent protein synthesis

What is the treatment for the management of bacterial hospital accquired pneumonia (HAP) with CURB-65 score of 3-4 (2)?

**Penicillins + Macrolides** * SEVERE: tazocin (piperacillin-tazobactam) IV +/- gentamicin IV ## Footnote Penicillins e.g. amoxicillin – beta lactams that bind proteins in the bacterial cell wall to prevent transpeptidation Macrolides e.g. clarithromycin – bind to the bacterial ribosome to prevent protein synthesis

Outline the pathogenesis of viral respiratory infection.

1. **Highly pathogenic strains** (zoonotic) 2. **Absence of prior immunity** Innate immunodeficiency (e.g. IFITM3 gene variant) B cells (antibody- presumably local) T cells (correlate with peripheral levels?) 3. **Predisposing illness/conditions** Frail elderly COPD/asthma Diabetes, obesity, pregnancy etc.

How is the respiratory epithelium designed to resist infections (5)?

* **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.

What is antibody mediated immunity (humoral immunity) (2)?

* **Adaptive**, so dependent on prior exposure * **B cells activated** to differentiate into **antibody secreting plasma cells** * Different antibody classes provide different biochemical properties and functions

How is the nasal cavity and bronchi designed to resist infections (2)?

Outline the pathophysiology of viral respiratory infections.

What is the supportive therapy recommended for the management of viral respiratory infections (5)?

* **Oxygen** (for hypoxia) * **Fluids** (for dehydration) * **Analgesia** (for pain) * **Nebulised saline** (may help expectoration) * Chest **physiotherapy**

What is the preventative / prophylactic therapy recommended for the management of viral respiratory infections (1)?

* **Vaccines** * Major surface antigen – **spike protein** * **Viral vector** (e.g. adenovirus vaccine e.g. Oxford/AZ) * **mRNA vaccines** (e.g. BioNtech/Pfizer)

What is the treatment recommended for the management of viral respiratory infections (2)?

**Anti-inflammatory** * Dexamethasone (steroids) * Tocilizumab (anti-IL-6R) or Sarilumab (anti-IL-6) **Anti-virals** * Remdesivir – broad spectrum antiviral – blocks RNA-dependent RNA polymerase activity * Paxlovid – antiviral protease inhibitor * Casirivimab and imdevimab - monoclonal neutralising antibodies for SARS-CoV-2

What anti-inflammatory medication is recommended for the management of viral respiratory infections (3)?

* **Dexamethasone** (steroids) * **Tocilizumab** (anti-IL-6R) * **Sarilumab** (anti-IL-6)

What anti-viral medication is recommended for the management of viral respiratory infections (3)?

* **Remdesivir** – broad spectrum antiviral – blocks RNA-dependent RNA polymerase activity * **Paxlovid** – antiviral protease inhibitor * **Casirivimab and imdevimab** - monoclonal neutralising antibodies for SARS-CoV-2