Airway And Lung Diseases Flashcards
Dynamic evolution of asthma (3)
Brief Symptoms-Bronchoconstriction
Exacerbations AHR- Chronic airway inflammation
Fixes airway obstruction-Airway remodelling
Hallmarks of remodeling in asthma (3)
Thickening of basement membrane
Collagen deposition on submucosa
Hypertrophy of smooth muscle
Asthma- The clinical syndrome (9)
Episodic symptoms and signs Diurnal variability Non-productive cough Triggers Associated atopy increase in IgE (rhinitis, conjunctivitis, eczema) Blood eosinophilia >4% Responsive to steroids or beta-agonists Family history of asthma Wheezing due to turbulent airflow
Diagnosis of Asthma (5)
History and examination
Diurnal variation of peak flow rate
Reduced forced expiratory ratio (FEV1/FVC<75%)
Provocation testing to trigger bronchospasms (exercise, histamine, methacholine, mannitol)
Reversibility to inhalation of salbutamol (>15%)
Components of COPD (3)
Mucociliary dysfunction
Inflammation
Tissue damage
Causes of airflow limitation in COPD
Mucous hypersecretion
Disrupted alveolar attachments
Inflammatory instruction
Characteristics of Chronic bronchitis in COPD (6)
Chronic neutrophilic inflammation Mucus hypersecretion Mucociliary dysfunction Altered lung microbiome Smooth muscle spasm and hypertrophy Partially reversible
Characteristics of Emphysema in COPD
Alveolar Destruction
Impaired gas exchange
Loss of bronchial support
Irreversible
Assessment of COPD
Assess symptoms
Assess degree of airflow limitation using spirometry (FEV<50% indicates high risk)
Assess risk of exacerbations (2 or more withing past year indicates high risk)
Assess comorbidities (IHD/HF)
Clinical Syndrome COPD (8)
Chronic symptoms-not episodic Smoking Non-atopic Daily productive cough Progressive breathlessness Frequent infective exacerbations Chronic bronchitis-wheezing Emphysema-reduced breath sounds
Causes of Thoracic Restriction outwith the lungs
Skeletal
Muscle weakness
Abdominal obesity/ascites
Skeletal causes of thoracic restriction
Vertebrae e.g. Thoracic kyphoscoliosis, Ankylosing spondylitis
Ribs e.g. Traumatic multiple rib injury
Muscle weakness causes of thoracic restriction
Intercostal or diaphragmatic e.g. myaesthenia gravis, guillan barre, motor neurone disease, poliomyelitis
Classification of DLPD (5)
Acute DLPD
Episodic DLPD (all of which may present acutely)
Chronic DLPD due to occupational or environmental hazards/drugs
Chronic DLPD with evidence of systemic disease
Chronic DLPD without evidence of systemic disease
Causes of fluid in alveolar air spaces
Cardiac pulmonary oedema Non-cardiac pulmonary oedema Infective pneumonia Infarction Alveolitis Dust-disease Carcinomatosis Eosinophilic Other causes - rheumatoid disease, drugs, cryptogenic
Types of alveolitis in DLPD
Extrinsic-Allergic-Alveolitis Sarcoidosis Drug induced alveolitis Toxic gas/fumes Pulmonary fibrosis Autoimmune
Clinical syndrome of DLPD
Breathless on exertion Cough but no wheeze Finger clubbing Inspiratory Lung crackles Central cyanosis (if hypoxaemic) Pulmonary fibrosis
Types of drugs for airway obstruction (2)
Preventers (anti-inflammatory)
Relievers (bronchodilators)
Corticosteroids
Anti-inflammatory drugs used in asthma and COPD
Oral steroid
E.g. Prednisolone
Low therapeutic ratio
Only used for acute exacerbations not for maintenance
Inhaled steriod
E.g.Beclomethasone
High therapeutic ratio
Used for maintenance monotherapy in asthma
Used in ICS/ LABA combo in COPD not as monotherapy
Reduces exacerbations in eosinophilic COPD
What is the risk of using corticosteroids for COPD
May cause pneumonia in COPD due to local immune suppression & impaired mucociliary clearance
Especially with fluticasone due to prolonged lung retention
What size must particles be to enable them to travel down past the carina?
<5 microns
What size must particles be to get past the 7th generation of bronchial tree?
<2microns
Actions of a spacer device (6)
Avoids coordination problems with pMDI
Reduces oropharyngeal and laryngeal side effects
Reduces systemic absorption from swallowed fraction
Acts a holding chamber for aerosol
Reduces particle size and velocity
Improves lung deposition
Cromones
Only used in asthma (eg Cromoglycate)
Mast cell stabiliser - weak anti-inflammatory cf steroids
Cromoglycate effective in atopic children (EIB)
Inhaled route only
Not used much due to poor efficacy
Leukotriene receptor agonists
Anti-inflammatory used in asthma
E.g. Montelukast - oral route, once daily, high therapeutic ratio
Less potent anti-inflammatory than inhaled steroid
2nd line: complimentary non steroidal anti-inflammatory additive to inhaled steroid
Effective in EIB
Also effective in allergic rhinitis ( with anti-histamine )
Anti-IgE monoclonal antibody
E.g. Omalizumab (Xolair)
Inhibits the binding to the high-affinity IgE receptor Inhibits TH2 response and assoc mediator release from basophils/mast cells
Injection every 2-4 weeks for asthma only
For patients with severe persistent allergic asthma (raised IgE) despite max therapy.
Very expensive
Little effect on pulmonary function but reduces exacerbations and oral steroid sparing effect
Anti-IL5
Mepolizumab (Nucala )/Reslizumab (Cinquero)
Blocks the effects of the TH2 cytokine IL-5 which is responsible for eosinophilic inflammation in asthma
Injection every 4 weeks –for asthma only
For patients with severe refractory eosinophilic asthma (raised blood eosinophils >4%) – despite max therapy
Very expensive
Little effect on pulmonary function or symptoms but reduces exacerbations and oral steroid sparing effect
B2-agonists
Stimulate bronchial smooth muscle B2-receptors
Bronchodilators
Short-acting - salbutamol
Long-acting – bid :salmeterol/formoterol
Used in asthma [as ICS/LABA dual ]
Used in COPD [as ICS/LABA dual or LAMA/LABA dual or ICS/LABA/LAMA triple ]
High therapeutic ratio when given by inhaled route
Systemic B2 effects when given systemically or at high inhaled doses
Combination inhalers
Beclometasone/formeterol
Single Maintenance And Reliever Therapy
Muscarinic antagonists (anticholinergics)
Muscarinic antagonists (aka Anticholinergics)
Block post junctional end plate M3 receptors
Short acting: Ipratropium
Long acting: Tiotropium,Glycopyrronium, Umeclidinium, Aclidinium
Inhaled route only - high therapeutic ratio
Used mostly in COPD to reduce exacerbations
Also used in asthma as triple therapy at step 4 (only tiotropium) as ICS/LABA/LAMA
High nebulised doses of ipratropium used in acute COPD and in acute asthma
Methylxanthines
Anti-inflammatory/ Bronchodilator
Used in asthma and COPD
Oral Methylxanthine
Theophylline for maintenance therapy
Sustained release formulation useful for nocturnal dips
Used as add to inhaled steroid as complimentary non steroidal anti-inflammatory
IV methylxanthine
Aminophylline for acute attacks
Non selective phosphodiesterase inhibitor
Also act as adenosine antagonist
Low therapeutic ratio -metabolised by P450 in liver
PDE4 inhibitors
Roflumilast oral tablet
Indicated for COPD only
Minimal effect on FEV1 –anti-inflammatory action
Reduces exacerbations –additive to LABA or LAMA
Adverse effects : Nausea/Diarrhoea/Headache/Weight loss
Mucolytics
Oral carbocisteine , erdosteine
To reduce sputum viscosity and aide sputum expectoration [and reduce exacerbations ] in COPD
Rarely used –only as add on to other treatments
Aims in treatment of chronic asthma (7)
Abolish symptoms, Minimise B2-use, Normalise FEV1, Reduce PEF variability, Reduce exacerbations, Prevent long term airway remodeling Avoid triggers
Treatment of chronic asthma
Suppress inflammatory cascade with inhalatory steroid
+/- Non steroid anti-inflammatory therapy –eg theophylline ,anti-leukotriene,cromoglycate
+/- Stabilise smooth muscle with LABA/LAMA
Treatment of acute asthma
Oral prednisolone (or iv hydrocortisone ) Nebulised high dose salbutamol, ± Neb ipratropium, ± iv aminophylline/magnesium At least 60% O2 ITU Assisted mechanical intubated ventilation if falling PaO2 and rising PaCO2
Aims of treatment of COPD
Reduce exacerbations
Improve pulmonary function
Improve QOL
Prevent pulmonary heart disease
Treatment of COPD
Smoking cessation Immunisation Pharmacotherapy Pulmonary rehab Oxygen
Acute Treatment of COPD
Nebulised high dose salbutamol + ipratropium
Oral prednisolone
Antibiotic (amoxycillin/doxycycline) if infection
24-28% O2 titrated against PaO2/PaCO2
Physio to aide sputum expectoration
Non invasive ventilation to allow higher FiO2
ITU Intubated assisted ventilation only if reversible component (eg pneumonia)
Effort dependent pulmonary function test
Forced expiratory volumes/flow rates
Effort independent pulmonary function test
Relaxed vital capacity -spirometry Helium/N2 washout static lung volumes Whole body plethysmography Impulse Oscillometry Exhaled breath nitric oxide
Gas diffusion tests
CO transfer factor
Arterial blood gases (resting)
SaO2 during exercise
Spirometry in patient with asthma
FEV1 reduced compared to normal patient
FEV same, just takes longer, so slope is reduced
Spirometry of COPD patient
Slope gradient more shallow compared to normal patient
FVC and FEV1 reduced
Ratio the same
Volume dependent expiratory airway closure
Asthma, chronic bronchitis
Pressure dependent expiratory airway closure
Emphysema
Bronchial challenge testing
Exercise
Methacholine/Histamine/Mannitol
Allergens/Chemicals
Exercise testing
FEV1 or PEF decrease post exercise - Asthma
Decreased SaO2 during exercise in interstitial lung disease
Transfer Factor (diffusing capacity)
CO diffusion across alveolar-capillary barrier
Single breath diffusing capacity
Measured as TLCO
To monitor treatment response in lung disease
Indications of decreased TLCO
Anaemia Emphysema Int lung disease Pulmonary oedema Po emboli Bronchiectesis
Airway resistance
Measured by either whole body plethysmography or more commonly/easily with impulse oscillometry
Useful in patients (eg kids) where easier to breathe at tidal volume than doing forced expiratory manoeuvre
Exhaled breath condensate
Exhaled breath nitric oxide measured at flow of 50ml/s
Non invasive marker of eosinophilic airway inflammation in asthma
Not useful in COPD as nitric oxide suppressed by smoking
High levels of exhaled NO (> 35ppb) reflect uncontrolled asthmatic inflammation
Used as an adjunct to bronchial challenge to assess asthmatic inflammation –especially when spirometry is normal
Haemoptysis
Coughing up blood
Can be a direct consequence of a primary tumour
Why is recurrent episodes of pneumonia considered a symptom of lung cancer?
A primary lung cancer can cause obstruction of bronchi
Stridor
A coarse, audible wheeze during inspiration
Symptoms arising from local invasion of the recurrent laryngeal nerve
Recurrent laryngeal nerve palsy
Symptoms arising from local invasion of the pericardium
Breathless
Atrial fibrillation
Pericardial effusion
Symptoms arising from local invasion of the oespohagus
Dysphagia
Symptoms arising from local invasion of the brachial plexus
Wasting of small muscles
Symptoms arising from local invasion of the pleural cavity
Pleural effusion
Symptoms arising from local invasion of the vena cava
Distended veins
Most common sites for metastases in lung cancer
Liver Brain Bone Adrenal Skin Lung
Paraneoplastic symptoms of lung cancer
Finger clubbing Hypertrophic pulmonary osteoarthropathy Weight loss Thrombophlebitis Hypercalcaemia Hyponatraemia Eaton Lambert syndrome
Thrombophlebitis
Blood clot
Can present as a red track
Hypercalcaemia
Stones (Renal/biliary calculi)
Bones (Bone Pain)
Groans (Abdominal pain, Constipation, N+V)
Thrones (Polyuria)
Psychiatric overtones (Depression, anxiety, reduced GCS, Coma)
Cardiac Arrythmia
Hyponatraemia (Syndrome of inappropriate antidiuretic hormone SIADH)
Results in low sodium concentration Nausea/vomiting Myoclonus Lethargy/confusion Seizures/coma
Possible Investigations for Lung Cancer
Chest X-ray CT scan of thorax PET scan Bronchoscopy Endobronchial Ultrasound (EBUS) Full blood count Coagulation screen Na, K, Ca, Alk Phos Spirometry, FEV1
Smoking associated types of lung tumour
Adenocarcinoma (35%)
Squamous carcinoma (30%)
Small cell carcinoma (25%)
Large cell carcinoma (10%)
What do adenocarcinomas express?
TTF (thyroid transcription factor) 1
What does SCC express
Nuclear antigen p63 and high molecular wt. cytokeratins
