resp Flashcards
features of asthma?
wheeze ±dry cough atopy/allergen sensitisation reversible airway obstructiom airway inflammation - eosinophils , type 2 lymphocytes
pathogenesis of asthma?
bronchial epithelium exposed allergen eg mild → inflammation → SM hypertrophy , ↑ ECM → airway remodelling
immune response ion asthma?
antigen presented to MHC II on APC → Th0 bind → Th2 → IL 4, 13, 5 → VCAM1 expression, ↑mast cells, IGE synthesis, mucin secretion, eosinophilic airway inflammation
how is allergic sensitaization tested for in asthma?
blood tests for specific IgE antibodies to allergens of interest
total IgE not sufficient
tests for eosinophilia?
blood eosinophil ≥300
sputum eosiniphil ≥2.5%
exhaled nitric oxide
what is FeNO used for?
asthma diagnosis
steroid responsiveness prediction
corticosteroid adherence
objective tests for asthma?
airway obstructi9on on spirometry - FEV1/FVC <0.7
reversible airway obstruction - bronchodilator , ≥12%
exhaled NO , ≥35 child, ≥40 adult
asthma management?
- ↓ inflammation - inhaled corticosteroids , leukotriene receptor antagonists
- acute relief - beta 2 agonists, anticholinergics (smooth muscle relaxation)
- severe asthma - anti-IgE antibody , anti-IL5 antibody / anti-IL5 receptor antibody
how do corticosteroids work?
↓ xcytokines ↓ eosinophils ↓ macrophages , dendritic cells ↓ leak from endothelial cells ↑ b2 receptors in SM ↓mucus secretion
most important of asthma management?
adherence to ICS
why do children with asthma often have prolonged illnesses?
↓ IFN a, B y → reduced antiviral responses
how does anti-IgE antibody therapy work?
binds to circulating IgE → cannot activate mast cells cells and basophils → stop allergic cascade
reduces IgE production over time
anti-IgE antibody?
omalizumab
indicati9ons for omalizumab?
severe persistent IgE asthma ≥6yrs old
4 or more oral corticosteroids in past year
documented compliance
serum IgE 30-1500
anti-IL5 antibody?
mepolizumab
function of IL5?
regulates growth recruitment activation and survival of eosinophils
mepolizumab indications?
severe eosinophilic asthma
blood eosinophils ≥300
4+ exacerbations requiring oral corticosteroids in past year
risk factors for lung cancer?
75-90
M≥F
lower SES
smoking
non smoking causes of cancer?
asbestos radon indoor cooking fumes chronic lung diseases eg copd, fibrosis immunodeficiency familial
4 types of lung cancer?
adenocarcinoma - peripheral, mucous tissue
squamous cell carcinoma - central, bronchial epithelium
large cell cancer
small cell cancer - pulmonary neuroendocrine cells
lung cancer oncogenes?
EGFR tyrosine kinase - adenocarcinoma, women, asian, never smoekrs
ALK tyrosine kinase & cROS1 receptor tyrosine kinase - NSCLC , young patients, never smokers
BRAF 1 - NSCLC, smokers !!
symptoms of lung cancer?
wt loss cough breathlessness fatigue chest pain haemoptysis or asymptomatic
features of advanced / metastatic lung cancer?
bone fain seizures , focal weakness clubbing hypercalacemia hyponatraime cushings horners syndrome pembertons sign (obstructed SVC) cachexia
imaging options for lung cancer?
chest XR
CT abdo chest for staging
PET scan for occult metastases
methods of biopsy for lung cancer>
central tumours - bronchoscopy
staging - endo-bronchial US and trasnbrocnhial needle aspiration of mediating lymph nodes
peripheral - CT guided lung biopsy
what’s used to determine patient fitness in lung cancer>
WHO performance status 0 -asymptomatic 1 - symptomatic but ambulatory 2 - symptomatic ≤50% day in bed 3- symptomatic ≥50% day in bed 4 - bedbound 5- death
radical treatment for 0-2
surgical management for lung cancer?
early stage disease standard care
lobectomy + lymphadenectomy
sublunar resection if stage 1
radical radiotherapy for lung cancer?
alt to surgery for early stage especially if comorbidity
stereotactic ablative body radiotherapy
systemic treatments for lung cancer?
oncogene-directed - metastatic NSCLC with mutation
immunotherapy - metastatic NSCLC with no mutation and PDL1 ≥50%
cytotoxic chemo - metastatic NSCLC with no mutation and PDL1 ≤50% (+immunotherapy)
treatment for metastatic NSCLC with mutation? example?
oncogene directed (EGFR, ALK, ROS-1) erlotinib, crizotinib (tyrosine kinase inhibitors)
treatment for metastatic NSCLC with no mutation and PDL1 ≥50↓? example
immunotherapy eg pembro/atezo lizumab
treatment for metastatic NSCLC with no mutation and PDL1 ≤50↓? examples?
cytotoxic chemo , platinum based eg carbo/cisplatin
+ immunotherapy
palliative care for lung cancer?
all with advanced stage disease symptom contorl psychological support education end of life planning
treatment options for lung cancer if locally advanced/lymph nodes involved?
surgery + adjuvant chemo
radio + chemo ± immunotherapy
symptoms of upper RTI?
cough sneezing runny nose sore throat headache
symptoms of lower RTI?
phlegm cough muscle aches wheezing bretahlessness fever fatigue
symptoms of pneumonia?
chest pain
blue lips
sever fatigue
high fever
commonest cause of infant mortality ≤1 yr?
lower RTIs esp RSV
risk factors for pneumonia?
age ≤2 / ≥65 smoking ↑↑alchohol contact with school aged children poverty /ovrcrowding ICS, PPIs, immunosuppressants COPD , asthma , diabetes, HIV, malignancy
common pathogens of respiratory infection?
bacterial : strep pneumoniae myxoplasma pneumoniae haemophilus pneumoniae mycobacterium tuberculosis
viral: influenza a or b RSV rhinovirus cornoviruses human metapneumovirus
common causes of CAP?
sterp pneumoniae* myxoplasma pneumoniae** staph aureus chlamydia pneumoniae** haemophilus influenzae*
- typical
- *aTYPICAL
common causes of HAP?
staph aureus * pseudomonas aeurignoas* klebsiella species e coli acinetobacter enterobacter*
*ventialtor
how is potential bacterial pneumonia graded?
CURB-65 score confusion resp rate ≥30 blood pressure ≤90 SBP / ≤60 DBP ≥65 urea≥7 if hospital
treatments for bacterial pneumonia?
oxygen fluids analgesia nebuliser saline penicillins macrolides
CURB-65 scores and treatments?
0 CAP - amoxicillin (/clarithromycin if pen allergic)
0 HAP - doxycycline PO
1-2 CAP - amoxicillin + clarithomycin
3-5 CAP - benzylpenicillin IV + clarithomycin PO (or teicoplanin)
severe HAP - tazocin IV ± gentamicin IV
strep pneumonia characteristics?
gram positive
extracellular
opportunistic (takes advantage of change in environment)
what is a pathobiont?
normally commensal microbe
wrong environment → pathology
how do viral infections result in disease?
not pathobionts
cause cellular inflammation , mediator release, local immune memory , damage epithelium → loss of cilia , bacterial growth, poor antigen barrier, loss of chemoreceptors
what causes severe viral disease?
highly pathogenic strains eg zoonotic
innate immunodefieicny - absence of prior immunity
predisposing condition
frail/elderly/pregnant
where does H1N1 influenzaA infect?
URT - haemogluttinin binds a2,6 sialic acids
where does H5N1 avian flu infect?
LRT - haemogluttinin binds a 2,3 sialic acids
where does SARS CoV2 infect?
spike proteins bind ACE in nasal epithelium and type 2 pneumocytes
defence mechanisms of respiratory epithelium?
tight junctions mucous linign and cilia clearance anitmicrobials pathogen recognition receptors interferon pathways - up regulate anti viral proteins
antibodies in nasal cavity?
IgA
epithelial cells have polyIgA receptor → export IgA to mucosal surface from plasma
homodimer very stable in protease rich environment
antibodies in bronchi?
IgG
thin walled alveoli allow transfer of plasma IgG into alveolar space
leading cause of infant hospitilaztion?
respiratory syncytial virus
RSV symptoms?
nasal flaring chest wall retractions hypoxemia cyanosis croupy cough wheezing on expiration prolonged expiration rales and rhonchi tachypnea apneic episodes
risk factors for RSV in oinfants?
premature birth
congenital heart and lung diseases
treatment options for SARS CoV2?
oxygen fluids analgesia dexamethasone tocilizumab remdesevir paxlovid monoclonal antibodies vaccines
what is the SRDS Berlin definition?
within 1 week of a known clinical insult or new or worsening respiratory symptoms
bilateral opacities on imaging not explained baby collapses, effusions, nodules
oedema not explained by cardiac failure/fluid overload
oxygenation - PEEP ≥5
PaO2/FIO2:
mild 200-300
moderate 100-200
severe ≤100
what can cause acute resp failure?
infection aspiration primary graft dysfunction after lung Tx trauma pancreatitis sepsis myasthenia Guillain-Barré syndrome
what can cause chronic resp failure?
copd fibrosis CF lobectomy muscular dystrophy
what can cause acute on chronic resp failure?
infective exacerbation of COPD/CF
myasthenia crises
post operative
what is type I resp failure? causes?
hypoxemic , PAO2 < 60
increased shunt fraction, alveolar flooding
collaspe aspiration pulmonary oedema fibrosis pulmonary embolism pulmonary hypertension
what is type II resp failure? causes?
hypercapnic, pacCO2 ≥ 45
decreased alveolar minute ventilation ,↑ dead space ventilation
muscle failure, airway obstruction, chest wall deformity
what is type III resp failure? causes?
perioperartive resp failure
low functional residual capacity → ↑ atelectasis
hypoxaemia or hypercapnia
posture, incentive spirometry, analgesia, anaesthetic technique
what is type IV resp failure? causes?
shock → poor perfusion
patients are ventilated and intubated
causes of ARDS?
pulmonary : aspiration trauma inhalation burns surgery drugs infection
extra pulmonary : trauma pancreatitis burns trasnfusion sx BM trasnplant drugs infection
what responses cause acute lung injury?
leucocyte activation and migration → macrophages and neutrophils DAMP releaae - HMGB1 , RAGE cytokine release , IL-6,8,1B, IFN-y cell death TNF signalling via TNFR-1
management for resp failure?
treat underlying cause: bronchodilators, pulmonary vasodilators steroids Abx, antivirals plasma exchange, ritixumab
resp support:
oxygen, nebulisers, ventilation, ECMO
multiple organ support:
CV
renal
immune therapies
sequelae of ARDS?
poor gas excahnge
infection →sepsis
inflammation
systemic effects
specific interventions for ARDS?
resp support
intubation and ventilation
mechanical intervention
pronation
imaging for ARDS?
CT- lung recruitment
lung USS
scoring system for ARDS?
Murray score = average score of all 4: PaO2/FiO2 CXR PEEP Compliance
0=normal
1-2.5 = mild
2.5-3 = severe
≥3 = ECMO
ECMO inclusion criteria?
severe resp failure with non-cardiac cause , Murray score ≥ 3
pH ≤ 7.2
positive pressure ventilation is inappropriate
reversible disease process, unlikely to lead to prolonged disability
ECMO exclusion criteria?
significant comorbidity
would be life dependent on ECMO
contraindicated to continuation of active support
issues with ecmo?
time to access geographical inequity obtaining access clotting/bleeding costs
how can exercise capacity be evaluated?
cardiopulmonary exercise test - cycle ergometer/treadmill
six minute walk test
incremental shuttle walk test
top 3 causative agents of resp infection?
human rhinovirus
influenza a/b
s pneumoniae
