Asthma, CF, bronchiectasis Flashcards
How do you check for bronchial hyperresponsiveness in asthma?
Bronchial challenge test
When may it be appropriate to check for bronchial hyperresponsiveness in asthma?
If clinical features are atypical or where the dx has important implications (defence force employment, athletes)
Unnecessary if variable airflow obstruction has already been documented
What does a high serum eosinophil count in asthma suggest?
Likely to be responsive to ICS or monoclonal ab
What does a high exhaled nitric oxide level mean in asthma?
Allergic inflammation
Likely to respond to steroids
What’s Samter’s triad?
Asthma
Aspirin intolerance - triggers asthma
Nasal polyps
How does allergic bronchial pulmonary aspergillus (ABPA) present?
Difficult to control asthma Recurrent pulmonary infiltrates Recurrent infections not responsive to abx Bronchiectasis with thick sputum Very high IgE (>1000IU/ml) Evidence of aspergillus hypersensitivity
What is allergic bronchial pulmonary aspergillus (ABPA)?
Hypersensitivity response to the fungus, aspergillus
Occurs in asthma and CF
Rx allergic bronchial pulmonary aspergillus (ABPA)
Steroids
How does eosinophilic granulomatosis with polyangiitis (EGPA) present?
Symptoms vary from mild to life threatening
But almost everyone has asthma +/- nasal polyps and high eosinophils
Multi-organ disease - peripheral neuropathy, mononeuritis multiplex, skin disease, cardiac disease
Rx eosinophilic granulomatosis with polyangiitis (EGPA)
Steroids
MTX, mycophenolate, cyclophosphamide
Mepolizumab (reduce eosinophils)
Explain the stepwise management of asthma
Step 1
ICS-fomoterol PRN
Step 2
Daily ICS-fomoterol + PRN same
Step 3
Daily low dose ICS-LABA + PRN SABA
Step 4
Daily medium dose ICS-LABA + PRN SABA
Step 5
Daily high dose ICS-LABA +/- add on therapy + PRN SABA
What are some potential add on therapies in severe asthma?
Tiotropium - useful in frequent exacerbations, airflow obstruction
Macrolides (azithromycin) - useful in frequent exacerbations, cough + sputum
Montelukast - useful in aspirin sensitive
Monoclonal abs - useful in frequent exacerbations
When is omalizumab indicated in asthma?
Targets IgE
Allergic asthma
Used in addition to ICS + LABA
When are mepolizumab and benralizumab used in asthma?
Targets IL5
Eosinophilic asthma
What is bronchiectasis?
Permanent dilation of bronchi and bronchioles due to destruction of airway muscles and elastic connective tissue
Causes of bronchiectasis
- Post-infectious (e.g. pertussis)
- ABPA
- COPD
- Traction secondary to fibrosis (radiological dx)
- Aspiration
- Obstruction
- Immunological defects (primary, secondary)
- Congenital defects (Marfan’s, ciliary defects, A1AT deficiency)
- Inflammatory - RA, coeliac disease, SLE, IBD
- Young’s syndrome
- Amyloidosis
- CF
Exacerbating comorbidities: GORD/aspiration, non-tuberculous mycobacterium, sinus disease
Investigations in bronchiectasis
- CT chest - look for tree and bud and granulomatous nodules - might indicate non-tuberculous mycobacterium
- Sputum x3 - AFB to look for non-tuberculous mycobacterium
- ABPA - IgE and aspergillus precipitants
- Immunoglobulins - if isolated level of IgG, can receive IV gammaglobulins which can reduce exacerbations
- 6MWT
- ABGs
Consider
- CF genotyping
- ECHO
- Bronchoscopy
- Immune test including HIV
- Nasal brushings to exclude coeliac syndrome
- Gastroscopy to exclude GORD
What are the organisms commonly implicated in bronchiectasis?
- Pseudomonas - important player. Very hard to eradicate.
- Non-tuberculous mycobacterium
- Aspergillus
- Stenotrophomonas nalophilia
- Staph aureus
Rx bronchiectasis
- Treat the cause
- Improve airway clearance/chest physio/pulmonary rehab
- Treat infection (acute and chronic) - PO ciprofloxacin or IV beta-lactam +/- aminoglycoside
- Treat airway obstruction - salbutamol +/- ICS. 2nd line ICS/LABA, theophylline, tiotropium.
- Treat chronic inflammation - erythromycin, azithromycin. 2nd line doxycycline. 3rd line nebulised tobramycin.
- Inhaled hypertonic saline - can be trialled in frequent exacerbators or has significant symptoms due to viscous mucous (be careful if FEV<1L due to bronchospasm)
Less common
- Surgical resection
- Lung transplant
- Bronchial artery embolization for significant haemoptysis
What must you monitor if using macrolides long-term for bronchiectasis?
Monitor sputum for resistance and increased non-tuberculous mycobacterium
Monitor ECG for prolonged QT
Pathophysiology of CF
Defect in the cystic fibrosis transmembrane conductance regulator (CFTR)
CFTR is blocked in CF –> can’t transport Cl out of cell –> Enac tries to compensate by transporting Na into cell to neutralise Cl –> dehydrated airways + viscous mucous
What are the 6 functional classifications of CFTR mutations?
1) No protein
2) No traffic (most common phenotype due to homozygous DF508 genotype)
3) No function (gate doesn’t open properly) due to G551D genotype
4) Less function
5) Less protein (minor abnormality)
6) Less stable (minor abnormality)
How is CF diagnosed?
1) Meconium ileus at birth
2) Heal prick test - high sensitive, low specificity
3) Sweat test - chloride >60mmol/L, borderline 40-60mmol/L
4) Gene testing - 50 panel test; but >2000 mutations
How does CF affect the lungs?
CFTR protein defect –> unable to secrete chloride –> sodium follows and stays inside cell –> thick secretions –> infection –> inflammation –> bronchiectasis –> lung destruction
Treatment options for CF
1) CFTR modulators
Ivacaftor - CFTR potentiator - opens the channel of the protein
Tezacaftor - CFTR corrector - moves the protein onto the cell surface
Elexacaftor - CFTR corrector - moves the protein onto the cell surface
Different combinations available for homozygous/heterozygous DF508 mutations
Ivacaftor available for G551D mutations
Improves FEV1 and reduces exacerbation
2) Inhaled DNase
- Improves FEV1
3) Azithromycin
4) Inhaled abx - tobramycin, colistin
4) Inhaled mucolytics - hypertonic saline, mannitol
- Improves FEV1
5) Inhaled bronchodilators
6) Lung transplant (less common now)
Common pathogens in CF
1) Children
2) Adults
1) Staph aureus
2) Haemophilus, pseudomonas
Why is it important to treat pseudomonas colonisation aggressively in children with CF?
To prevent chronic infection due to its ability to cause resistance, form mature biofilms which makes it hard for abx to penetrate
What are some strategies to get rid of pseudomonas colonisation?
Long-term oral abx
Long-term nebulised abx
Airway clearance
?Inhaled DNAse to break up biofilms
What are the 2 types of non-tuberculous mycobacterium often seen in CF?
1) MAC
- Usually seen in older people
- Mild disease
2) Mycobacterium abscessus
- More advanced disease with a rapid decline in lung function
- Active infection is contraindicated in transplant
Clinical guidelines suggest annual screening for NTM
Even if NTM is grown in sputum culture, it does not mean there is NTM lung disease. Most people with single positive culture will not require treatment. The decision to treat will depend on symptoms, or when there is a lack of response to treatment of typical CF infections.
Rx non-tuberculous mycobacteria in CF
Very difficult!!
Often resistant to abx.
Will usually require 3 abx for 12 months+
Clinical features of CF (other than lungs)
1) Pancreatic insufficiency (90% will have this)
- Due to thickened pancreatic secretions –> activation of proteolytic enzyme –> autodigestion
- Most will require pancreatic enzymes for life
2) GI
- Meconium ileus (neonate)
- Distal intestinal obstruction syndrome (adults) - thick secretions block the ileo-caecal junction. May present with faecal mass in RIF mimicking appendicitis. Rx colonlytely, gastrograffin, may require laparotomy
- GORD
- Rectal prolapse
- Intussusception
3) Bone disease
- Dexa every 2 years
- Rx: calcium, vitamin D, bisphosphonates
4) Infertility
- Males: absent vas deferns
- Females: can generally conceive but may have dehydrated secretions –> fallopian tube adhesions, slow passage of oocyte to uterus
5) Mental health
What’s a bronchial provocation challenge?
Gold standard for asthma diagnosis. Picks up bronchial hyperresponsiveness.
- Gets done when RFTs are inconclusive but symptoms are suggestive of asthma
DIRECT challenge Deliver noxious stimuli that acts on SM receptors (histamine and methacholine) Positive test: 21% fall in FEV1 Sensitive but not specific Lots of false positives
OSMOTIC INDIRECT challenge
Detect the presence of inflammatory cells in the airways
Hypertonic saline, exercise and mannitol
Positive is 15% or more reduction in FEV1
More specific but not sensitive
What’s cardiopulmonary exercise testing?
Do it on bicycle or treadmill
Cardiac, pulmonary and muscle assessment
Work patients to target HR or workload
For people with SOB with unknown cause
Also done pre-pneumectomy to determine suitability
Measures
VO2 (ability to extract oxygen by the muscle; increases lineally with workload; good sign of physical fitness or functional aerobic capacity; VO2 can go up as you get fitter; HR drops as you go fitter)
VCO2
Minute ventilation (VE)
What’s your maximum heart rate?
Age-30
HR is the most important physiological change which contributes to decline in VO2 with age
What’s maximal voluntary ventilation?
FEV1 x 40
We all have ventilatory reserve but having lung disease reduces the maximum voluntary ventilation
2 types of bronchiectasis
Focal
One lobe only
Diffuse
More than one lobe
Causes of focal bronchiectasis
Something is blocking or narrowing a specific airway
But not lung ca - grow too quickly to develop bronchiectasis
Foreign body
Slowly growing tumour
Lymphadenopathy
Twisting or displacement of airways after a lobar resection
Next best test for focal bronchiectasis
Bronchoscopy
Looking for the endoluminal problem that is contributing to the bronchoscopy
Causes of diffuse bronchiectasis
Infections
- Postviral (adenovirus, measles, influenza, pertussis, varicella, HIV)
- Mycobacterium
- ABPA
- Severe bacterial infections
Congenital conditions
- CF
Immunodeficiency conditions
- CVID
Rheumatological conditions
- 30% RA have bronchiectasis
Toxin or drug exposure
- Chlorine inhalation
Diffuse bronchiectasis involving upper lobe
DDx
CF
ABPA
Sinus disease (bad) and bronchiectasis
Loss of sense of smell
Young person
Primary ciliary dyskinesia
Primary ciliary dyskinesia
What is it?
Diagnosis
Autosomal recessive
Variable penetrance
Absent cilia (extreme; dexta cardia) or shortened cilia or cilia that don’t move properly
Ciliary motility study - nasal swab with microscope to look at cilia and their movements
Or sometimes diagnosed in sinus surgery
Primary ciliary dyskinsia
Clinical features
Sinusitis is way more severe than bronchiectasis
Recurrent OM in adults!!
Compared to CF - bronchiectasis disease is equal to sinus disease
When do you suspect CF in adults with bronchiectasis?
Age <40
Upper lobe disease
FHx of recurrent chest infections/CF
S.aureus in sputum
Diagnosis of CF in suspected adults
CF genetic panel (as the genetic abnormalities are mild)
Not the sweat test
Conditions associated with bronchiectasis
Primary hypogammaglobulinaemia CLL Myeloma Chemotherapy All cause low IgG --> can result in bronchiectasis
Rheum
RA
SLE
Sjogren’s
MANAGEMENT bronchiectasis
Sputum clearance techniques
- PEP device
- No postural drainage due to reflux risk for adults
Treat acute exacerbations
- Volume change, colour change
- Treat for 2 weeks
Suppress microbial load - Prophylaxis - Rules #Bronchiectasis #Pseudomonas #2 or more chest infections/year - Oral macrolides (antiinflammatory effects, reduce sputum volume, inhibit biofilm layer, colony forming units) or nebulised aminoglycosides (gentamycin or tobramycin)
Treat underlying condition
E.g. immunoglobulin therapy for low IgG
Reduce excessive inflammatory response
- Consider ICS for obstructive picture/reversibility
Control bronchial haemorrhage
Surgical removal of segments/lobes
One test to do in bronchiectasis
Sputum MCS
Look for pseudomonas - damaging to the airways and make the disease progress
This is a gamechanger
Asthma severity is defined by
Control
NOT lung function
Difficult to treat asthma is
those remained uncontrolled with high dose ICS
Severe asthma is
Subset of difficult to control asthma
Asthma that remains uncontrolled despite high dose ICS + LABA + leukotriene modifier or theophylline for the previous year OR
Treatment with oral corticosteroid for at least half the previous year
OR asthma that requires such treatment in order to remain well controlled
4 questions to ask to assess control of asthma
1) Day time symptoms
2) Need for reliever
3) Limitation of activity
4) Sx at night or on waking in the middle of the night
0 = good control 1-2 = partial control 3 = poor control
Reasons for poor control asthma
RSV Influenza Beta blockers even eyedrops NSAIDs Chinese medicine Dust mites Mould Mouldy hay (aspergillus loves this - Farmer's lung, interstitial pneumonitis) Thunderstorm asthma Canola URT inflammation - allergic rhinitis GORD
Less common
CF
ABPA
EGPA
Treatment mild asthma
Minimal symptoms
Well controlled of low dose ICS
Need treatment = remodelling of airways
Must have low dose ICS to prevent exacerbation (people who died from thunderstorm asthma were either not on ICS cause symptoms were mild or were not compliant with their ICS)
Treatment difficult to treat and severe asthma
High dose ICS/LABA
Others
Tiotropium in severe asthma
Macrolides (antiinflammatory)
LT modifier (montelukast) - use only in aspirin related asthma and polyps
Biologics
- Must fulfil clinical, medication and investigation criteria
- Poorly controlled asthma and mainly in eosinophilic allergy phenotypes
- Works extremely well
- Omalizumab (anti IgE)
- Mepolizumab (anti-IL5)
- Benzalizumab (anti-IL5)
- Dupilimab (anti-IL4)
Theophylline - not recommended anymore
Types of asbestos
Horrible fiber and brilliant insulator
Blue more likely to cause mesothelioma
How long from exposure to asbestos related lung disease?
Latency period if long between exposure and development of asbestos related lung disease (often 30-40 years)
5 types of asbestos related lung disease
Pleural plaques Asbestos related pleural disease Asbestosis Mesothelioma Lung cancer (NSCLC, squamous cell)
Pleural plaques are
Calcium forming asbestos fibers
Benign NOT premalignant Asymptomatic Can't affect lung function Marker of asbestos exposure
Asbestos related pleural disease
Diffuse pleural disease
More than 25% circumference showing pleural disease
Benign
NOT pre malignant
Can cause symptoms if there is enough circumference involved causing restrictive process
Rounded atelectasis
Pleural wrapping around normal lung
Can look like lung mass
Must be immediately adjacent to pleura
Need to have other evidence of asbestos related pleural disease (>25% circumference involvement)
Crows feet (lines around the mass)
May not even need biopsy if very characteristic on CT
Asbestosis
Interstitial lung disease associated with asbestos
Requires to the most prolonged asbestos exposure
Starts in upper lobes then moves down
Often men >60yo
Which asbestos related pleural disease requires the most prolonged asbestos exposure?
Asbestosis
How do you differentiate between asbestosis and IPF?
Both often men over age 60
Asbestosis
- Decades of working with asbestos (must have long exposure)
- Similar age of fibrosis on CT
- Upper lobe predominant
IPF
- Temporal heterogeneity on CT (pathognomic) - varying ages of fibrosis i.e. some areas with lots of architectural distortion and other areas with little architecture distortion
- Lower lobe predominant
- They could have plaques from working with asbestos
Mesothelioma
How do they present?
Pleural effusion
Chest wall pain (not pleuritic; dull ache that keeps them up at night) - this is due to neural invasion of this tumour into nerve endings into pleura and chest wall
If they have previous asbestos exposure, they have mesothelioma until proven otherwise
Mesothelioma diagnosis
- CXR: one big lung, one small lung late stage
- CT: irregular edges around mediastinum and around lung
Pleural tap will NOT diagnose mesothelioma (all you get is atypical mesothelioma cells which can happen in parapneumonic effusion)
To make the diagnosis, its VATS biopsy. Usually do pleurodesis at the same time.
Mesothelioma requires how much asbestos exposure?
Usually long exposure
But can be short exposure too - 1-2 days is enough
Mesothelioma treatment
Immunotherapy Pemetrexed (chemo) - prolong survival by a few months only
Average life expectancy is 12 months. Will just wrap around every thing mediastinum, oesophagus.
Not curable
Do you try eradicate pseudomonas in bronchiectasis?
No
They always have inflammation and sputum in their airways so can’t be eradicated. But can reduce the colony forming units in exacerbations.
Different to other lung disease.
How do you treat exacerbation of bronchiectasis (pseudomonas)?
2 weeks
2 agents
PO ciprofloxacin + nebulised aminoglycosides
What is ABPA?
Need either asthma or bronchiectasis to start with
Breathes in aspergillus fiber –> allergic to it (profound IgE response in airway)
ABPA diagnostic criteria
Asthma or bronchiectasis
Raised IgE
Positive aspergillus precipiant (blood test)
Aspergillus on sputum culture or bronchoscopy
Proximal upper lobe bronchiectasis (chronic)
ABPA classic scenarios
Classic presentations
1) Asthmatic who normally has a dry cough, starts coughing up sputum plugs
2) Bronchiectasis patient who normally coughs up sputum, but suddenly develops wheeze
ABPA treatment
Prednisolone (IgE mediated disease) - course duration varies 3/12+
Itraconazole can shorten duration of exacerbation
Can recur
>1 episode: lifelong itraconazole
CF bronchiectasis has higher prevalence of aspergillus
True of false
True
Common peroneal nerve palsy Asthma Eosinophilia Cardiac myopathy Dx
EGPA
EGPA management
Pulse methylpred 3/7
+ immunosuppressant (depending on organ involvement)
E.g CYC for cardiac involvement
ANCA neg more likely to have cardiac disease and more severe
Can asbestos related pleural disease look like mesothelioma?
Yes
Meso wraps around mediastinum thats quite distinct
Thats why you need a biopsy (VATS)
Don’t get chest wall pain in asbestos related pleural disease
What’s SMART protocol in asthma?
LABA in symbicort has onset of action 2 min
Has been shown to reduce oral corticosteroid in 12 month period
BUT need good health literacy
Most common lung cancer related to smoking
Squamous cell carcinoma
Biologics in asthma
Do they cause cancer or immunosuppression?
Don’t cause cancer or immunosuppression
Very specific anti-IgE, IL5, eosinophilic agents
Theres 15 year data on mepolizumab
Is IPF inflammatory?
No
Its all fibrotic
Won’t have ground glass changes unlike interstitial pneumonitis, organised pneumonia
Problems with putting a chest drain into mesothelioma pleural effusion
Cancer may seed through the drain
Consider giving radiotherapy to that site to prevent seeding
Exercise induced asthma management
Still need low dose asthma
Thunderstorm asthma
Occurs in Spring
Allergic to rye grass
Before the rain
Rye grass pollenating –> winds before the storm that sweeps the pollen into the clouds –> Lightening/electricity opens up the pollen spores –> breath in spores –> bronchospasm
Mostly relates to people who don’t know they have asthma and just have hayfever
Turn off airconditioners
Close windows
Turn the vents inwards inside cars
