respiratory infections Flashcards
What are symptoms of an upper respiratory tract infection?
Cough, sneezing, runny/stuffy nose, sore throat, headache
What are symptoms of a lower respiratory tract infection?
Productive cough (phlegm), muscle aches, wheezing, breathlessness, fever, fatigue
What are symptoms of pneumonia?
Chest pain, blue tinting of lips, severe fatigue, high fever
What are DALYs and what is 1st in global DALYs?
Disability adjusted life years (sum of years of life lost to disability). Acute lung infection is 1st.
What affects morality burden from respiratory infections?
Increasing age (eg above 70)
What are the demographics of pneumonia?
Rates increase with age and more in men
Who is at high risk of respiratory infections?
Very young (children under 5) and very old.
What contributes to infant mortality?
Mix of viral & bacterial causes of respiratory illness. Pneumonia & brochiolitis.
What are risk factors for pneumonia?
Age under 2 or above 65, smoking, alcohol, contact with kids under 15, poverty, overcrowding, taking inhaled ICS, immunosuppressants, PPIs, COPD, asthma, heart disease, liver disease, diabetes, HIV, malignancy, hyposplenism, complement of Ig deficiencies, risk factors for aspiration, previous pneumonia. Specific factors: geographical variations, animal contact, healthcare contacts
What are some causative agents for respiratory infections? Which are the most common?
- viral - human rhinovirus (v. common), influenza A or B, human metapneumovirus, respiratory syncytial virus (RSV), coronavirus 2. bacteria - streptococcus pneumoniae (common), mycoplasma pneumoniae, heamophilus influenzae & myobacterium tuberculosis. Viral is most common, then bacterial only, then mix of bacterial - viral.
What are bacteria causing community acquired penumonia?
Streptococcus pneumoniae (common), mycoplasma pneumoniae, stalphylococcus aureus, chlamydia pneumoniae, haemophilus influenzae
What are examples of typical bacteria causing pneumonia?
Streptococcus pneumoniae, haemophilus influenzae, moraella catarrhalis
Which is the most common bacteria causing pneumonia and its features?
Streptococcus pneumoniae. Gram-positive, extracellular, opportunistic pathogen
What are bacteria causing hospital acquired pneumonia?
Staphylococcus aureus, pseudomonas aureginosa, kiebsiella species, E.coli, acinetobacter, enterobacter
What are bacteria causing ventilator associated pneumonia?
Pseudomonas aureginosa (most common), staphylococcus aureus, enterobacter
What are examples of atypical bacterial organisms causing pneumonia? What are features of this kind of infection?
Mycoplasma pneumoniae, chalmydia pneumoniae, legionella pneumophilia. Slow growing, persistent cough for long time, never quite clear it.
What is the mechanism of damage of acute bacterial pneumonia?
Inflammation & swelling of alveoli. Alveolar cells get disrupted. Systemic & local inflammation puts strain on CV system too.
What is bronchitis and bronchiolitis?
Bronchitis - inflammation of bronchi. Bronchiolitis - inflammation of bronchioles
How do you grade potential bacterial pneumonia? What does each score mean?
CURB-65 score (1 point for each): confusion, respiratory rate > 30 breaths/min, blood pressure <90 systolic or 60 diastolic, 65 or older. In hospital add urea >7mmol/L. ).
0: low severity (home treatment, antibiotics), 1-2: moderate (consider hospital referral), 3-4 high severity - urgent hospital admission & empirical antibiotics if life-threatening
What are supportive treatments for bacterial pneumonia?
Oxygen (hypoxia), fluids (dehydration) analgesia (pain), nebulised saline (helps expectoration), chest physiotherapy
How do penicillins work + example?
Beta lactams that bind proteins in bacterial cell wall to prevent transpeptidation. Eg. amoxicillin
How do macrolides work + example?
Bind to bacterial ribosomes to prevent protein synthesis eg. clarithromycin
What is the duration of antibiotics given for bacterial pneumonia?
5-7 days (7-14 days if atypical)
What is the key to increasing success of antibiotics? What do you do in severe pneumonia?
- time to administration (every hour in septic shock reduces survival chance by 8%) 2. effective antibiotics - (typical CAPs may respond to penicillin, atypicals may need macrolides. If severe pneumonia give everything initially based off severity and then culture)
How do you catch bacterial pneumoniae?
From yourself. In oropharynx we have haemophilus pneumoniae, staphylococcus aureas, streptococcus peumoniae. In nose we also have streptococcus pneumoniae.
What is the human microbiome?
Trillions of microbial cells populate body at every barrier surface
What is the microbiota?
Ecological communities of microbes found inside multi-cellular organisms
What are commensal microbes?
Microbes living in symbiotic relationship with host providing nutrients with suitable ecological niche
What are opportunistic pathogens?
Takes advantage of change in conditions (often immuno-suppression)
What is a pathobiont?
Normally commensal but when found in wrong environment can cause pathology
How do viral infection result in disease?
Primarily attack epithelial cells in tract, replicate, causing davage to epithelium, which can lead to loss of cilia function (more prone to bacterial growth), poor barrier to antigen, loss of chemoreceptors. Can cause immune response, cell inflammation (mediator release, local immune memory). If large immune response can cause damage.
What causes severe disease?
- highly pathogenic strains (zoonotic).
- absence of prior immunity (innate immunodeficiency of IFITM3 gene variant), B cells, T cells
- predisposing illnesses/conditions: frail elderly, COPD/asthma, diabetes, obesity, pregnancy etc
What is viral tropism and what does this affect?
Viral tropism refers to ability of viruses to infect one specific place (where they bind affects pathology).
Where does SARS-COV-2 bind?
SARS-COV-2 spike protein binds ACE2 (we have high ACE2 in nasal epithelium (increased in smokers) and in Type 2 pneumocytes (increased in smokers)
Where does H1N1 influenza A bind?
Haemagglutinin binds a2,6 sialic acids (found higher up in tract)
Where does H5N1 avian flu bind?
Haemaglutannin binds a,2,3 sialic acids (found lower in tract)
What are the respiratory epithelial cells and their role?
Target and first line of defence. First barrier against infection, but also target for replication.
How does the structure of the respiratory epithelium defend against pathogens?
- tight junctions to prevent systemic infection
- mucous lining & cilial clearance prevents attachment and clears particulates
- antimicrobials - recognise, neutralise or degrade microbes & their products
- pathogen recognition receptors recognise pathogens inside or outside cell
- interferon pathways activated by viral infection promotes upregulation of anti-viral proteins & apoptosis
What are serotypes and their implications? Which virus has many?
Serotypes are viruses that cannot be recognized by serum (antibodies) that recognise another virus. Rhinovirus has 100+
What is an antigen?
Any molecule against which antibodies can be generated
What antibody class is most present in upper respiratory tract and what does it do?
High IgA. Ecs express poly IgA receptor allowing export of IgA to mucosal surfaces. Homodimer is extremely stable in protease rich envirnment.
- Binds, aggregates and neutralises threat (good because don’t want too much inflammation)
What antibody class is most present in lower respiratory tract and what does it do?
High IgG. Thin walled alveolar space allows transfer of IgG into alveolar space. It is inflammatory but good at killing pathogens
What are the advantages and disadvantages of influenza?
+No reinfection by same strain.
- Imperfect vaccines, annual needed, mainly homotypic immunity, vaccine immunity wanes quickly (need to predict what next flu will look like)
What is RSV (respiratory syncytial virus) and its disadvantages?
Recurrent reinfection with similar strains. No vaccine, poor immunity to infection, short-lasting
What are the problems with SARS-COV2?
No prior immunity. New vaccine - waning immunity, potential for re-infection, unclear vaccination regime
What are the differences/similarities between RSV and influenza?
RSV doesn’t care about prior immunity. Both mostly upper respiratory infection, similar pandemic trends
What does RSV do to infants? What are risk factors for it? What are symptoms?
- RSV causes bronchiolitis in infants.
- Leading cause of infant hospitalisation in developed world, half of kids infected in year 1 of life, all kids by year 3, 1% develop severe bronchiolitis, can repeatedly infect kids. Similar virsues induce hMPV & PIV.
- Risk factors: premature brith, congenital heart & lung disease.
- Symptoms: nasal flaring, chest wall retractions, hypoxaemia & cyanosis, croupy cough, expiratory wheezing, tachypnoea
How does RSV affect adults?
Can spread to them but rarely severe in adults
What supporting treatments should be used for respiratory infections?
Oxygen, fluids, analgesia, nebulised saline, chest physiotherapy
What preventative treatments should be used for respiratory infections?
Vaccines: major surface antigen spike protein, viral vector, mRNA vaccines
What therapeutic treatments should be used for respiratory infections?
Anti-inflammatory (dexamethasone- steroids), toclizumab (anti-IL6R), sarilumab (anti-IL6)
What anti-virals should be used for respiratory infections?
Remdesivir (broad spectrum - blocks RNA dependent RNA polymerase activity), paxlovid (antiviral protease inhibitor), casirivimab & imdevimab (monoclonal neutralising antibodies for SARS-COV2)
How are respiratory infections and chronic diseases associated?
- Viral bronchioltiis associated with development of asthma.
- Rhinoviruses most common cause of asthma & COPD exacerbations.
- Likely to get secondary bacterial pneumonia after viral infections
