Respiratory Flashcards
Define Chronic Bronchitis
Bronchitis means inflammation of the bronchial tubes in the lung.
It is said to be chronic when it causes a productive cough for at least 3 months each year for 2 or more years.
Epidemiology of Bronchitis
Usually co-exists with emphysema, causing COPD.
RF for Bronchitis
- Smoking
- Exposure to air pollutants e.g. sulfur and nitrogen dioxide
- Exposure to dust and silica
- Family history of chronic bronchitis
Pathophysiology of Bronchitis
The airways are exposed to all sorts of irritants and chemicals.
This can result in infiltration of the walls with inflammatory cells.
The epithelial layer may become ulcerated and, with time, squamous epithelium replaces the columnar cells (squamous metaplasia) when the ulcer heals.
The inflammation is followed by scarring and thickening of the walls, which narrows the small airways.
Also, the irritants stimulate hypertrophy and hyperplasia of the mucinous glands in the main bronchi, as well as the goblet cells in the bronchioles, which increases mucus production in both locations.
Since the bronchioles are smaller, even a slight increase in mucus can lead to airway obstruction, which contributes to the majority of the air trapping.
The reid index is a measurement (usually done post-mortem) to show the ratio of the thickness of the bronchial mucinous glands, relative to the total thickness of the airway - from the epithelium to the cartilage. Normally, this ratio should be less than 40%, but it can be over 40% for people with chronic bronchitis, due to hyperplasia and hypertrophy of the glands.
Also, smoking makes the cilia short and less mobile, making it harder to move mucus up and out of bronchioles. A cough is sometimes the only way to clear this mucus.
People with chronic bronchitis also often present with hypoxemia and hypercapnia. This is because the mucus plugs block airflow, causing high levels of CO2 and low levels of O2 in the lung so less O2 moves into blood and less CO2 moves out of blood.
Blood vessels can then undergo vasoconstriction to shunt blood away from damaged tissue towards healthy lung tissue.
Overall, there is airway narrowing due to hyperplasia, inflammation and oedema.
Effects on FVC, FEV1, FEV1:FVC and TLC of COPD
In COPD, the airways become obstructed and the lungs don’t empty properly which leaves air trapped inside the lungs.
- FVC (max air exhaled in one breath): lowered
- FEV1 (first second of air breathed out in a single breath): lowered, more than the FVC
- FEV1:FVC ratio: lowered
- TLC (total lung capacity): increased due to air trapping
Signs of Bronchitis
- Wheeze: due to narrowing of the passageway available for air to move in and out
- Crackles or rales: caused by the popping open of small airways
- Cyanosis (blue bloaters): if there is buildup of CO2 in blood
Symptoms of Bronchitis
- Productive cough
- Dyspnoea
- Signs of CO2retention
- Drowsy
- Asterixis
- Confusion
Management of Bronchitis
Examples include:
- Smoking cessation
- Management of associated illnesses
- Antibiotics for infections
- Supplemental oxygen
- Bronchodilators
- Inhaled steroids
Complications of Bronchitis
- Cor pulmonale and right sided heart failure: vasoconstriction leads to pulmonary hypertension which affects the functioning of the right ventricle.
- Lung infections: can develop behind the mucus plugs
Define Emphysema
In emphysema, the alveolar air sacs become damaged or destroyed.
The alveoli permanently enlarge and lose elasticity, and as a result, individuals typically have difficulty with exhaling, which depends heavily on the ability of lungs to recoil.
Epidemiology of Emphysema
Usually co-exists with chronic bronchitis, causing COPD
RF for Emphysema
Smoking
Pathophysiology of Emphysema
Normally, oxygen flows out of the alveoli and into the blood while carbon dioxide makes the reverse commute.
When the lung tissue is exposed to irritants e.g. cigarette smoke, it triggers an inflammatory reaction.
Inflammatory reactions attract various immune cells which release inflammatory chemicals as well as proteases e.g. elastases and collagenases.
Normally, there is a low pressure environment in the airways and elastin in the walls prevents the lungs from collapsing inwards in this low pressure environment. This allows air to be exhaled out.
However, in emphysema, the elastin is lost which causes collapse. This results in:
- Air-trapping distal to the point of collapse
- The lungs becoming more compliant - when air is inhaled, the lungs easily expand and hold onto that air.
- Breakdown of the thin alveolar walls - septa. This reduces the surface area for gas exchange.
Over time, as more and more lung tissue is affected, emphysema can lead to hypoxemia.
This leads to hypoxic vasoconstriction to navigate blood flow away from damaged lung tissue.
Types of Emphysema
Types of emphysema:
Different types affect the acinus (endings of the lung containing alveoli) in different ways:
- Centriacinar emphysema: most common pattern. Only damages the central or proximal alveoli of the acinus. It also typically affects the upper lobes of the lungs. This is usually due to smoking.
- Panacinar emphysema: entire acinus is uniformly affected and typically affects the lower lobes of the lungs. Often associated with alpha-1 antitrypsin deficiency. Alpha-1 antitrypsin is a protease inhibitor and protects collagen and elastin. Without it, the proteases are able to break down the alveolar walls
- Paraseptal emphysema: distal alveoli of the acinus are most affected. Typically affects the lung tissue on the periphery of the lobules.
-
Irregular emphysema: scarring and damage that affects the lung parenchyma
patchily, independent of acinar structure
Signs of Emphysema
- Breathing with pursed lips (pink puffers): prevents alveolar collapse by increasing the positive end expiratory pressure
- Barrel shaped chest: due to air trapping and hyperinflation
- Loss of cardiac dullness:due to hyperexpansion of lungs from emphysema
- Downward displacement of liver:due to hyperexpansion of lungs from emphysema
- On imaging: increased anterior-posterior diameter, a flattened diaphragm, and increased lung field lucency
Symptoms of Emphysema
- Dyspnoea
- Cough: could be productive
- Weight loss: due to energy expenditure while breathing
- Signs of CO2retention
- Drowsy
- Asterixis
- Confusion
Management of Emphysema
Examples include:
- Smoking cessation
- Supplemental oxygen
- Bronchodilators
- Inhaled steroids
- Antibiotics: for secondary infections
Complications of Emphysema
- Pneumothorax: the distal enlarged alveoli in paraseptal emphysema can rupture and cause a pneumothorax.
- Cor pulmonale and right-sided heart failure: extensive vasoconstriction causes pulmonary hypertension and puts pressure on right ventricle
Define COPD
Chronic obstructive pulmonary disease (COPD) describes progressive and irreversible obstructive airway disease.
It is a combination of emphysema and chronic bronchitis.
Epidemiology of COPD
- There are 1.2 million people with COPD living in the UK
- COPD is the fourth leading cause of death globally
- Usually diagnosed >45 years
RF for COPD
- Age:usually diagnosed after the age of 45
- Tobacco smoking: the single greatest risk factor for COPD
- Air pollution
- Occupational exposure: such as dust, cadmium (in smelting), coal, cotton, cement and grain
- Alpha-1 antitrypsin deficieny: younger patients present with features of COPD
Pathophysiology of COPD
COPD is a combination ofemphysema and chronic bronchitis
- Emphysemainvolves loss of alveolar integrity due to an imbalance between proteases and protease inhibitors (e.g. alpha-1 antitrypsin) triggered by chronic inflammation, such as smoking, which causes elastin breakdown
- Bronchitisinvolves increased mucus secretion secondary to ciliary dysfunction and increased goblet number and size → lung parenchymal destruction → impaired gas exchange
In COPD, the airways become obstructed and the lungs don’t empty properly which leaves air trapped inside the lungs.
- FVC (max air exhaled in one breath): lowered
- FEV1 (first second of air breathed out in a single breath): lowered, more than the FVC
- FEV1:FVC ratio: lowered
- TLC (total lung capacity): increased due to air trapping
V/Q mismatch in regards to COPD
V/Q (ventilation perfusion) mismatch is partly due to damage and mucus plugging of smaller airways from the chronic inflammation and partly due to rapid closure of smaller airways in expiration owing to the loss of elastic support - this mismatch leads to a fall in PaO2 and increased respiration. Usually PaCO2 is unaffected until patient’s are unable to maintain their respiratory efforts. Buildup of CO2 leads to cyanosis.
At first, excess CO2 is the drive for respiration. As patient’s become desensitised to CO2, hypoxaemia becomes the drive for respiration.
Exacerbations of COPD
Exacerbations: patients are susceptible to exacerbations during which there is worsening of their lung function. Exacerbations are often triggered by infections and these are called infective exacerbations. (Refer to ‘other notes’ below)
Signs of COPD
- Tachypnoea
- Barrel chest
- Hyperresonance on percussion
- Quiet breath sounds and wheeze
- Pursing of lips during expiration: helps to prolong expiration to breathe out as much air as possible.
- Cyanosis
- Tar staining of fingers
- Loss of cardiac dullness:due to hyperexpansion of lungs from emphysema
- Downward displacement of liver:due to hyperexpansion of lungs from emphysema
-
Evidence of an exacerbation:
- Significant dyspnoea, wheeze and cough
- Coarse crepitations
- Pyrexia
- Evidence of cor pulmonale: e.g. peripheral oedema
Symptoms of COPD
-
Dyspnoea: particularly on exertionMRC dyspnoea scale is used to grade the severity of breathlessness:
- Breathlessness on strenuous exercise.
- Breathlessness on hurrying or slight hill.
- Walksslower than contemporarieson ground level due to breathlessness ORhave to stop to catch breath when walking at own pace.
- Stops to catch breath after 100 metres ORa few minutes of walking
- Breathlessness on minimal activity (dressing) or unable to leave the house due to breathlessness
- Productive cough
- Wheeze
- Chest tightness
- Weight loss: due to energy expenditure while breathing
- Signs of CO2retention
- Drowsy
- Asterixis
- Confusion
Primary investigations for COPD
- Diagnosis is usually based on clinical presentation:A diagnosis of COPD should be considered in any patient over 35 years old who are current or ex-smokers with one or more symptoms of COPD e.g. exertional breathlessness, recurrent sputum production, wheeze, ‘winter bronchitis’ or chronic cough
- Primary investigations
- Spirometry and bronchodilator reversibility (BDR): FEV1/FVC<0.70; bronchodilator will not reverse symptoms.
- Chest X-ray: flattened diaphragm, hyperinflation and bullae. Should also be performed to see if there is evidence of lung cancer.
- FBC: COPD causes chronic hypoxia which may result in secondary polycythaemia; also required to determine if eosinophilia is present.
- Calculate body mass index (BMI): as a baseline to later assess weight loss (e.g. cancer or severe COPD) or weight gain (e.g. steroids)
Management of COPD
-
General:
- Smoking cessation: offer nicotine replacement, varenicline or bupropion
- Pulmonary rehabilitation: for patients who are self-perceived as functionally disabled by COPD (e.g. MRC grade ≥3)
- Vaccinations: one-offpneumococcaland annualinfluenza
- Good diet and exercise: esp if obese
-
Key pharmacological management:
-
Bronchodilators
- SABA:short-acting beta-agonist (e.g. salbutamol)
- SAMA: short-acting muscarinic antagonist (ipratropium)
- LABA: long-acting beta-agonist (e.g. salmeterol)
- LAMA: long-acting muscarinic antagonist (e.g. tiotropium)
- ICS: inhaled corticosteroid (e.g. beclometasone)
-
Bronchodilators
Complications of COPD
- Pulmonary hypertension and cor pulmonale: chronic hypoxia leads to pulmonary vasoconstriction and hypertension. The right side of the heart has to pump against high pressures and eventually fails.Clinical features include peripheral oedema, raised JVP, hepatomegaly, parasternal heave and a loud P2
- Pneumothorax:common due to bullae formation, resulting in a secondary spontaneous pneumothorax
-
Respiratory failure: type 1 or type 2
- Normal pCO2withlow pO2indicatestype 1 respiratory failure(onlyoneis affected)
- Raised pCO2withlow pO2indicatestype 2 respiratory failure(twoare affected)
- Exacerbation:usually due to bacterial or viral infection
- Secondary polycythaemia: chronic hypoxia induces polycythaemia
- Infections: people with COPD are more prone to infections
Prognosis for COPD
In 2012, 5.3% of all UK deaths were due to COPD, with over 90% of COPD-related deaths occurring in the over-65s age group.
Smoking cessation is the most important intervention in improving survival in stable COPD.
Other factors that improve survival in stable COPD include long term oxygen therapy (if appropriate) and lung volume reduction surgery (if appropriate).
Investigations for exacerbation of COPD
- ABG: shows respiratory acidosis (low PH and increased retention of CO2); increased bicarbonate suggests compensation by the kidney
- Chest xray:to look for pneumonia or other pathology
- ECG:to look for arrhythmia or evidence of heart strain (heart failure)
- FBC:to look for infection (raised white cells)
- U&E:to check electrolytes which can be affected by infection and medications
- Sputum culture:if significant infection is present
- Blood cultures:if septic
Management of exacerbation of COPD
Requires additional therapy above the baseline medications
If well enough to remain at home:
- Prednisolone30mg once daily for 7-14 days
- Regularinhalersor homenebulisers
- Antibioticsif there is evidence of infection
In hospital:
- Nebulised bronchodilators(e.g. salbutamol 5mg/4h and ipratropium 500mcg/6h)
- Steroids(e.g. 200mg hydrocortisone or 30-40mg oral prednisolone)
- Antibioticsif evidence of infection
- Physiotherapycan help clear sputum
Options in severe cases not responding to first line treatment:
- IVaminophylline
- Non-invasive ventilation(NIV)
- Intubationandventilationwith admission to intensive care
- Doxapramcan be used as a respiratory stimulant where NIV or intubation is not appropriate
Define Asthma
Asthma is a chronic inflammatory airway disease characterised by intermittent airway obstruction and hyper-reactivity.
There are 2 types:
- Allergic/ eosinophilic: allergens and atopy
- Non-allergic/ non-eosinophilic: e.g. exercise, cold air and stress
Epidemiology of Asthma
- Asthma is a common disease with a prevalence of almost 10% in the US
- Commonly starts in childhood between the ages 3-5 years and may either worsen or improve during adolescence
- Peak prevalence between 5-15 years
RF for Asthma
- History of atopy: such as eczemaand allergic rhinitis (IgE-mediated atopic conditions)
- Family history
- Allergens: such as tobacco smoke, pets, outdoor air pollution, weeds, grass, pollen and dust mites
- Viral upper respiratory tract infection
- Other triggers: cold weather and exercise, medications e.g. beta blockers and aspirin
- Occupational exposure (10-15%): isocyanates are the most common cause ofoccupational asthma(e.g. spray painting). Other causes include flour (bakers), platinum salts, soldering flux resin, glutaraldehyde and epoxy resins. These particularly affect people involved in plastic, foam and glue manufacturing. Requires a specialist referral.
Pathophysiology/Aetiology of Asthma
In asthma there is often an excessive reaction from Th2 cells against specific allergens.
Allergens from environmental triggers e.g. cigarette smoke, are picked up by dendritic cells and presented to Th2 cell. This leads to production of cytokines e.g. (IL-3, IL-4, IL-5, IL-10, IL-13)
This leads to the production of IgE antibodies which coat mast cells and stimulate them to release granules containing things e.g. histamines, leukotrienes and prostaglandins.
It also results in the activation of eosinophils which promote an immune response by releasing more cytokines and leukotrienes.
Minutes after the exposure to the allergen, smooth muscle around the bronchioles start to spasm and there is increased mucus secretion. This narrows the airways making it difficult to breathe.
There is also an increase in vascular permeability and recruitment of additional immune cells from the blood. A few hours after exposure, these immune cells, release chemical mediators that physically damage the endothelium of the lungs.
Initially these inflammatory changes are completely reversible, but over the years irreversible changes start to take place, leading to thickening of the epithelial basement membrane, which permanently reduces the airway diameter.
Asthma is thought to involve a complex interaction between genetic and environmental factors:
- Genetic susceptibilitypredisposes patients toairway hyper-responsiveness, triggered by environmental factors such as viral infection, allergens (the main cause in children), cold and exercise
- Genes controlling the production of cytokines IL-3,-4,-5,-9 & -13
- ADAM33 is associated with airway hyper-responsiveness and tissue remodelling
- In general, causes of childhood asthma diagnosed before age 12 are thought to be due to a stronger genetic influence, whereas later onset asthma is more likely to be largely due to environmental factors.
- The hygiene hypothesis: reduced early immune-system exposure to bacteria and viruses might increase the risk of later developing asthma, possibly by altering the overall proportion of immune cell subtypes.
Signs of Asthma
- Diurnal PEFR variation: worse at night and early morning
- Dyspnoea and expiratory wheeze
-
Samter’s triad
- Nasal polyps
- Aspirin insensitivity
- Asthma
Symptoms of Asthma
- Episodic shortness of breath: diurnal variation (worse at night and early morning)
- Dry cough
- Wheeze and ‘chest tightness’
- May be sputum
- History of exposure to a trigger
Primary investigations of Asthma
- Fractional exhaled nitric oxide (FeNO):>40 ppb is positive in adults
-
Spirometry:FEV1/FVC <70% suggests obstruction. If obstruction is found, BDR should be carried out
- Bronchodilator reversibility (BDR): improvement of FEV1 by ≥12%andincrease ≥200ml in volume post-bronchodilator
Stepwise management for asthma
Step 1: Newly diagnosed asthma -
SABA
Step 2: Not controlled on previous step OR newly diagnosed asthma with symptoms >3/week or night time waking -
SABA + low dose ICS (e.g. Budesonide)
Step 3:
SABA + low dose ICS + LTRA (e.g. montelukast)
Step 4:
SABA + low dose ICS + LABA (e.g. salmeterol)
If it gets worse add MART or LAMA or theophylinine
Complications of asthma
- Asthma exacerbations:typically triggered by an upper respiratory tract infection, pneumonia, or exposure to a trigger, e.g. an allergen or occupational exposure
- Pneumothorax
- Oral thrush: due to steroid medication
Prognosis for asthma
The life expectancy of controlled asthma is similar to the general population.
Remission rates are low and usually seen in mild cases.
Define Asthma exacerbation
An asthma exacerbation is an acute or subacute episode of progressive worsening of symptoms of asthma, including shortness of breath, wheezing, cough, and chest tightness.
Pathophysiology of asthma exacerbation
Asthma is a chronic, reversible obstructive airway disease. The onset is typically in childhood but often persists into adulthood.
Patients with asthma have hyperreactive airways which, in response to certain triggers, can undergo bronchoconstriction and inflammation, with excessive mucous secretion.
The inflammatory response is complex but is usually driven by Th2 cells, particularly if the trigger is an allergen.
The result of this is an asthma exacerbation, also known as acute asthma.
Key triggers:
- Known diagnosis of asthma
- Allergen exposure:pollen, dust mite, pets
- Occupationalexposures:plastics, foam, glue, flour
- Viral infection
- Smokingexposure
- Pollution
- Exercise
General clinical manifestations of Asthma exacerbation
- Progressively worsening shortness of breath
- Use of accessory muscles
- Fast respiratory rate (tachypnoea)
- Symmetrical expiratory wheeze on auscultation
- The chest can sound “tight” on auscultation with reduced air entry
Signs of Moderate asthma exacerbation
PEFR 50-75%
Signs of Severe Asthma exacerbation
Any of the following:
- PEFR 33-50%
- Respiratory rate ≥ 25
- Heart rate ≥ 110
- Inability to complete sentences in one breath
Signs of Life-threatening asthma exacerbation
Any of the following in a patient with severe asthma:
- PEFR < 33%
- SpO2< 92%
- PO2< 8 kPa
- PCO2normal (4.0-6.0 kPa)
- Altered consciousness
- Exhaustion
- Arrhythmia
- Hypotension
- Cyanosis
- Silent chest: no wheeze. This occurs when the airways are so tight that there is no air entry at all.
- Poor respiratory effort
Signs of near fatal asthma exacerbation
High pCO2 (> 6.0 kPa) and/or requiring ventilation with raised inflation pressures.
Investigations for asthma exacerbation
-
Peak flow expiratory rate (PEFR)
- Moderate:> 50-75% of baseline or predicted
- Severe:33-50% of baseline or predicted
- Life-threatening:< 33% of baseline or predicted
- ABG:patients will initially have respiratory alkalosis. Abnormal or high PCO2is an extremely concerning sign as it implies patient is tiring.
- Inflammatory markers:raised CRP and WCC may suggest an infective trigger
- CXR:hyperexpansion +/- a focus of infection
Management of asthma exacerbation in a patient with moderate asthma
- Moderate asthma: treated in primary care with
- Inhaled salbutamol
- 5-day course of prednisolone
Immediate management for severe or life threatening asthma exacerbation
- Oxygen:aim for SpO294-98%
-
Nebulised bronchodilators:
- Salbutamol 5mg is first-line and if the patient fails to improve, it can be given continuously.
- Ipratropium bromide 0.5mg can be given additionally every 4-6 hours
-
Corticosteroids:
- Prednisolone 40mg OD or
- 100mg hydrocortisone IV if the oral route is not tolerated (e.g. vomiting or reduced consciousness)
- Patients should continue on their inhaled corticosteroid
Subsequent management for severe or life threatening asthma exacerbation
f the patient does not respond to the above:
- IV bronchodilator:magnesium sulphate (first-line)
- ICU admission:if the patient is not responding to the above therapy, they may need ICU admission for further IV bronchodilation (salbutamol or aminophylline) and possible intubation
When to discharge a patient following a Severe asthma exacerbation
- Patients can be discharged once their PEFR > 75%
- Patients should be discharged with a course of oral steroids, inhaled steroids, and inhaled bronchodilator
- They must have a GP appointment within 48 hours of discharge and should be given an asthma plan
Complications of asthma exacerbation
- Intubation:those who fail to respond to medical therapy will require ICU admission and intubation
- Death:respiratory failure can lead to death. Three people die from asthma everyday in the UK
Prognosis for asthma exacerbation
In 2017, approximately 1,500 people died from asthma in the UK. On average, 3 people die every single day from asthma. The UK has one of the highest asthma-related death rates in Europe.
Define Lung cancer
Lung cancer is the uncontrolled division of epithelial cells which line the respiratory tract.
The majority of lung cancers are primary bronchial carcinomas. These are categorised into small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC).
Epidemiology of lung cancer
- Lung cancer is the third most common cancer in the UK behind breast and prostate.
- Lung cancer accounts for 35,000 deaths within the UK alone, which is more than breast and colorectal cancer combined.
- Lung cancers are strongly associated with smoking.
- Slightly more common in men than women but incidence in women is increasing due to women smoking habits
RF for lung cancer
- Increasing age: adenocarcinomas are an exception, often occurring in younger patients.
- Smoking: tobacco smoking or environmental smoke exposure.
- Other environmental exposure: radon, asbestos, arsenic, chromium, air pollution and radiation.
- Family history: some gene mutations are known to be associated with an increased risk of lung cancer development.
Pathophysiology of small cell lung cancer
- 15%of lung cancer cases
- Location: central lesion near the main bronchus
- Derived from neuroendocrine Kulchitsky cells
- Contain neurosecretory granules that can release neuroendocrine hormones. This makes SCLC responsible for multiple paraneoplastic syndromes:
- SIADH → hyponatraemia
- Ectopic ACTH→ Cushing’s syndrome
- Lambert-Eatonmyasthenic syndrome
- Rapid growth and patients usually present in an advanced stage
What % of lung cancers are NSCLC
85%
Patho of Lung Squamous cell carcinoma
- Location: central lesion
- Squamous, or square shaped, cells that produce keratin
- Paraneoplastic syndromes:Hypertrophic pulmonary osteoarthropathy: causes inflammation of the bones and joints in the wrists and ankles, and clubbing of the fingers and toesPTHrP→ hypercalcaemia
Patho of Lung Adenocarcinoma
- Location: peripheral lesion
- Originate from mucus-secreting glandular cells
- Paraneoplastic syndromes:Hypertrophic pulmonary osteoarthropathy: causes inflammation of the bones and joints in the wrists and ankles, and clubbing of the fingers and toesGynaecomastia
Patho of Large cell carcinoma of Lung
- Location: peripheral lesion commonly, but found throughout lungs
- Lack both glandular and squamous differentiation
- Paraneoplastic syndromes:Hypertrophic pulmonary osteoarthropathy: causes inflammation of the bones and joints in the wrists and ankles, and clubbing of the fingers and toesEctopic β-HCG secretion
Pathophysiology of Lung Carcinoid tumours
- Rare
- From mature neuroendocrine cells
- Paraneoplastic syndrome:Carcinoid syndrome which causes the secretion of hormones, particularly serotonin, which leads to increased peristalsis and diarrhoea, and bronchoconstriction causing asthma.
Pathophysiology of Bronchoalveolar cell tumours
- Location: found throughout lungs
- Not related to smoking
- Can cause significant sputum production
Signs of lung cancer
- Reduced breath sounds and a fixed monophonic wheeze may be present
- Stony dull percussion: suggests a malignant pleural effusion
- Supraclavicular or persistent cervical lymphadenopathy
-
Extrapulmonary manifestations:
- Clubbing: strongly associated with squamous cell carcinoma
- Facial plethora and swelling: due to superior vena cava obstruction
- Hoarseness: due to recurrent laryngeal nerve palsy (Pancoast tumour)
Symptoms of Lung cancer
- Persistent cough +/- haemoptysis
- Dyspnoea
- Pleuritic chest pain
- Recurrent pneumonia
- Constitutional symptoms as the body mounts an immune response against the cancer cells:
- Fever
- Weight loss and anorexia
- Night sweats
- Lethargy
Primary investigations for lung cancer
-
Chest X-ray: first-line
- Hilar enlargement
- Lung consolidation
- “Circular opacity” – a visible lesion in the lung field
- Pleural effusion – usually unilateral in cancer
- Collapse
- CT chest with contrast:gold-standard imaging; requested if there is an abnormal CXRorpersistent symptoms with a normal CXR.
-
PET-CT:if CT is suggestive of malignancy, patients should have a staging PET-CT
- 18-fluorodeoxygenase is preferentially taken up by malignant tissue
- PET-CT increases thediagnostic sensitivityof local and distant metastasis inNSCLC
- Biopsy:peripheral lesionsare biopsied under image guidance (percutaneously), andcentral lesionsvia bronchoscopy and endobronchial ultrasound
Staging for Lung cancer
TNM
General management for Lung cancer
- Smoking cessation
- Pain management
- Endobronchial treatment with stents or debulking can be used as part of palliative treatment to relieve bronchial obstruction caused by lung cancer.
Management of SCLC
- Surgery not usually offered as people with SCLC usually present late with advanced disease. Surgery is only appropriate for avery smallsubset of patients with early disease (T1-2a, N0, M0).
- Limited disease (confined to ipsilateral hemithorax):chemoradiotherapy with platinum-based agents, e.g. cisplatin
- Extensive disease:chemoradiotherapy with platinum-based agents, or palliative chemotherapy.
Management of NSCLC
-
Non-metastatic disease (stage I-IIIa):surgery, usually with adjuvant chemotherapy
- Typically involves lobectomy or pneumonectomy. Segmentectomy or wedge resection (taking a segment or wedge of lung to remove the tumour) is also an option.
- Removal of lymph nodes, if affected
- Curative radical radiotherapycan be used as an alternative to surgery
- Metastatic disease (stage IIIb and above):palliative treatment with immunotherapy, chemotherapy, and radiotherapy
Complications of Lung cancer
-
Local obstruction:
- Recurrent laryngeal nerve palsypresents with a hoarse voice. It is caused by the cancer pressing on the recurrent laryngeal nerve as it passes through the mediastinum.
- Phrenic nerve palsydue to nerve compression; causes diaphragm weakness and presents as shortness of breath.
- Superior vena cava obstruction caused by direct compression of the tumour on the superior vena cava. It presents with facial swelling, difficulty breathing and distended veins in the neck and upper chest. “Pemberton’s sign” is where raising the hands over the head causes facial congestion and cyanosis. This is a medical emergency.
- Horner’s syndromeis a triad of partial ptosis, anhidrosis and miosis. It is caused by aPancoast’s tumour(tumour in thepulmonary apex) pressing on thesympathetic ganglion.
-
Metastatis: e.g. to hilar lymph nodes, lung pleura, heart, breasts, liver, adrenal glands, brain, and bones.
- Adrenal: Addison’s disease
- Liver: hepatomegaly
- Bone: hypercalcaemia
- Brain: focal neurological deficit
-
Paraneoplastic syndromes:
- Syndrome of inappropriate ADH(SIADH) caused byectopic ADHsecretion by asmall cell lung cancerand presents withhyponatraemia.
- Cushing’s syndromecan be caused byectopic ACTHsecretion by asmall cell lung cancer.
- Hypercalcaemiacaused byectopic parathyroid hormonefrom asquamous cell carcinoma.
- Hypertrophic pulmonary osteoarthropathy: causes inflammation of the bones and joints in the wrists and ankles, and clubbing of the fingers and toes
- Limbic encephalitis: small cell lung cancer causes the immune system to make antibodies to tissues in the brain, specifically the limbic system, causing inflammation in these areas. This causes symptoms such as short term memory impairment, hallucinations, confusion and seizures. It is associated with anti-Hu antibodies.
- Lambert-Eaton myasthenic syndrome: small cell carcinoma prompts the body to produce autoantibodies which bind and destroy neurons. This leads to weakness, particularly in the proximal muscles but can also affect intraocular muscles causing diplopia (double vision), levator muscles in the eyelid causing ptosis and pharyngeal muscles causing slurred speech and dysphagia (difficulty swallowing).
- Renal: nephrotic syndrome
-
Haematological:
- Hypercoagulability: increased risk of venous thromboemboli
- Disseminated intravascular coagulation
Prognosis of lung cancer
Prognosis for lung cancer is poor, with a 10-year survival rate of 5.5%.
SCLC has a poorer prognosis than NSCLC, as SCLC patients will likely have disseminated disease at the point of first presentation.
Large cell lung carcinomas are anaplastic, poorly differentiated tumours with a poor prognosis.
Define Mesothelioma
Malignant mesothelioma is an aggressive epithelial neoplasm arising from the lining of the lung, abdomen, pericardium, or tunica vaginalis.
Epidemiology of Mesothelioma
- 45,221 deaths from mesothelioma were reported in the US between 1999 and 2015
- Often presents in patients >60 years old due to a latent disease period
- M>F
RF for Mesothelioma
- Increasing age: often presents in patients >60 years old due to a latent disease period
- Male gender
- Asbestos exposure: construction/demolition work, dock/shipyard work, electricians, plumbers, painters and carpenters.Crocidolite (blue asbestos)has the highest risk.
- Other causes: include radiotherapy, genetics, simian virus 40
Pathophysiology of Mesothelioma
Mesothelioma is an epithelial malignancy of themesothelial cells of the pleuracovering the lungs (and epithelial cells of other organs).
The primary cause of mesothelioma isasbestos exposure, with the development of the malignancy occurring 20-40 years after exposure (after a long latent period).
The asbestos fibres make their way to the mesothelium and can get tangled up with the cell’s chromosome. Asbestosis also believed to result in macrophage and neutrophil activation, consequently generating reactive oxygen and nitrogen species.
This causes DNA damage and modification in gene expression, thus increasing the risk of cancer.
Over time, small cancerous growths (mesothelial plaques) start to cover the visceral pleura over the lungs and the parietal pleura under the chest wall. These growths start to express a lot of calretinin, a calcium-binding protein, involved in regulating calcium levels within the cell.
Asbestos exposure causes a spectrum of disease, frompleural plaques andthickening toasbestosis, mesotheliomaandlung cancer.
Because asbestos fibers affect epithelial cells, they can cause mesothelioma in nearly any of the body’s internal organs, but it’s most commonly found in the lungs and abdominal organs - the liver, spleen and bowel - or in very rare cases, the pericardium lining of the heart and testes.
The lymphatics may also be invaded, causing hilar node metastases.
Signs of Mesothelioma
- Finger clubbing
- Reduced breath sounds
- Stony dull percussion: suggests a pleural effusion
- Ascites: if peritoneal disease is present
- Signs of metastases: e.g. lymphadenopathy, hepatomegaly, bone pain/ tenderness, abdominal pain/obstruction
Symptoms of Mesothelioma
- Shortness of breath
- Cough
- Pleuritic chest pain or chest wall pain
- Bloody sputum: if blood vessels are affected
-
Constitutional symptoms:
- Fatigue, fever, night sweats, weight loss
Primary investigations for Mesothelioma
- CXR:unilateral pleural effusion, reduced lung volumes, pleural thickening, lower zone interstitial fibrosis for asbestos
- Contrast-enhanced CT chest:performed following a suspicious CXR and may demonstrate**pleural thickening, pleural plaques and enlarged lymph nodes
Management for Operable Mesothelioma
Surgery
- Extrapleural pneumonectomy
- Pleurectomy with decortication (removing the pleural lining + tumour masses)
- Rarely curative
+/- Chemotherapy
- Cisplatin
- Pemetrexed
+/- Radiotherapy
Management for Inoperable Mesothelioma
Chemotherapy
- Cisplatin
- Pemetrexed
+/- Radiotherapy
Complications of Mesothelioma
- Pneumothorax: a mesothelioma can destroy the lung tissue between the bronchial tree and the pleural space, leading to air in the pleural space
- Local invasion of structures:dysphagia; hoarseness; cord compression; Horner’s syndrome
- Metastasis: metastases to the contralateral lung, peritoneum and brain
Prognosis of Mesothelioma
The prognosis for mesothelioma is very poor, as only 5-10% of patients live beyond 5 years after their diagnosis. The median survival is only 12 months.
Define Pulmonary embolism
Pulmonary embolism (PE) refers to obstruction of the pulmonary vasculature, secondary to an embolus.
RF/aetiology for PE
Virchow’s triad causing clots:
- Hypercoagulability: cancer, surgery (activates clotting cascade), oestrogen (pregnancy, contraceptive pill, HRT), nephrotic syndrome, sepsis, thrombophilia (factor V leiden mutation, protein C and S deficiency, antiphospholipid antibody syndrome)
- Venous stasis: recent surgery, DVT, immobility (long-haul travel/ hospitilisation), >60 yrs of age, obesity, other co-morbidities e.g. heart failure
- Endothelial damage: lower limb trauma, previous VTE, venous surgery, infections, toxins e.g smoking
- Rarer causes:
- Right ventricular thrombus (post-MI)
- Septic emboli (right-sided endocarditis - bacterial vegetation)
- Fat embolism (due to long bone fracture)
- Air embolism
- Amniotic fluid embolism
- Neoplastic cells
- Parasites
- Foreign material during IV drug misuse
Pathophysiology of PE
Emboli typically originate in the lower extremities, most commonly secondary to a deep vein thrombosis (DVT) in the calf:
Once the clot has formed, the increased pressure in the vein can cause a part of the main clot to break free, becoming a thromboembolus which can travel downstream towards the heart and gets into the right atrium, and then into the right ventricle to get pumped into the lungs where it can get lodged.
When a pulmonary embolism happens, a blockage in any of the arteries leads to a decrease in blood flow to lung tissue downstream.
If there is no blood flowing past an alveoli, then this means that the alveoli getting ventilated with fresh air but not getting perfused with blood. This is called a ventilation perfusion mismatch or a V/Q mismatch. The body needs oxygenated blood to function and can therefore only tolerate a bit of a V/Q mismatch, before the lungs are no longer able to meet the needs of the body.
After some hours, the non-perfused lung no longer produces surfactant resulting in alveolar collapse which in turn exaggerates hypoxaemia.
Signs of PE
-
Hypoxia
- Cyanosis may be present
- Deep vein thrombosis: swollen, tender calf
- Pyrexia may be present
- Tachypnoea and tachycardia
- Crackles
- Hypotension: SBP <90 mmHg suggests a massive PE
- Elevated JVP: suggests cor pulmonale
- Right parasternal heave: suggests right ventricular strain
Symptoms of PE
- Pleuritic chest pain
- Dyspnoea
- Cough +/- haemoptysis
- Fever
- Fatigue
- Syncope: a red flag symptom
Primary investigations of PE
- CXR:performed to rule out alternative pathology. It is typically normal in a PE, although a wedge-shaped opacification may be seen
-
ECG:
- Sinus tachycardia
- RBBBandright axis deviationsuggest right heart strain
- S1Q3T3: large S wave in lead I; large Q wave in lead III; inverted T-wave in lead III (a classic finding but only in 20% of patients)
- CT pulmonary angiogram (CTPA): highlights the pulmonary arteries to demonstrate any blood clots.
- D-dimer:detect fibrin breakdown products
Wells score for PE
Above 4 - High probability of PE
4 or below - Low probability of PE
Clinical signs and symptoms of a DVT - 3
PE is the number one diagnosis or equally likely - 3
Tachycardia (over 100bpm) - 1.5
Immobilised for more than 3 days or surgery in previous 4 weeks - 1.5
Previous objectively diagnosed PE or DVT - 1.5
Haemoptysis - 1
Malignancy with treatment within the last 6 months, or palliative - 1
What bacteria causes Whooping cough
Bordatella pertussis
How to treat whooping cough
Clarithromycin
Prevention for PE
- Compression stockings
- Frequent calf exercises during long periods of sitting still
- Prophylactic treatment with low molecular weight heparin
Supportive management for PE
- Admission to hospital
- Oxygen, as required
- Analgesia, if required
- Adequate monitoring for any deterioration
Management for Massive PE
-
Thrombolysis e.g. alteplase: injecting a fibrinolytic medication that rapidly dissolves clots. Can be done:
- Intravenouslyusing a peripheral cannula.
- Directly into thepulmonary arteriesusing a central catheter.
Management for Non-massive PE
Anticoagulation:
- Provoked:consider stopping anticoagulation at 3 months
- Unprovoked:consider continuing anticoagulationbeyond3 months.
- Interim anticoagulation: if a PE islikely(Well’s score >4) and investigations cannot be performed immediately, offer interim anticoagulation; if a PE isunlikely(Well’s score ≤4) and a D-dimer cannot be obtained within 4 hours, offer interim anticoagulation
Further management for PE
- Inferior vena cava filter:to stop clots from potentially moving into the heart and then the lungs
-
Surgical embolectomy:performed if thrombolysis is contraindicated or has failed
- Percutaneous catheter-directed thrombolysisis an alternative
Complications of PE
- Cor pulmonale:pulmonary vasculature obstruction can lead to pulmonary hypertension with subsequent right heart strain
- Pulmonary infarction:obstruction of the pulmonary vasculature can result in tissue necrosis
- Sudden death: if a large pulmonary thromboembolism happens at the pulmonary saddle, then it blocks blood from going to both lungs and can cause sudden death
- Respiratory alkalosis: hyperventilation as a response to the embolism causes rapid release of CO2 which can make the blood more alkali
- Embolic stroke: if patient has an atrial septal defect, embolus may enter left atrium and then left ventricle and travel to other parts of the body, including the brain
- Heparin-associated thrombocytopaenia:a side-effect of heparin therapy
Prognosis for PE
Less than 5 to 10% of symptomatic PEs are fatal within the first hour of symptoms. Haemodynamically stable patients have a lower mortality rate compared to those who present with cardiorespiratory arrest, which is associated with a very poor prognosis. Ultimately, the overall mortality at 3 months for an acute PE is 17%
Define TB
Tuberculosis (TB) is a granulomatous disease caused by Mycobacterium tuberculosis.
Epidemiology of TB
- 1.7 billion people worldwide have latent TB
- Common in South Asia and sub-Saharan Africa
- Prevalent in immunocompromised individuals
RF for TB
- Contactwith a person with active TB
- Endemic regions:South Asia or sub-Saharan Africa
- Homelessness
- Alcohol or drug abuse
- Immunocompromised: e.g. secondary to HIV, steroid use, malnutrition, immunosuppression medication
- Silicosis:impairs macrophage function
- Haematological malignancy
General pathophysiology of TB
Macrophages struggle to clear M. tuberculosis due to its waxy mycolic acid capsule which confers protection (the waxy membrane also prevents binding with normal stains - known as acid fastness).
The TB bacteria are very slow dividing with high oxygen demands (aerobes). It spreads via respiratory droplets from patients with active disease. After primary infection, immunocompetent patients can harbour the infection and remain asymptomatic (latent TB). In immunocompromised patients, reactivation and failure to contain the bacteria can manifest as secondary TB. It can then spread systemically, resulting in miliary TB.
Difference between primary, latent, secondary and miliary TB
Primary - first exposure, often asymptomatic
Latent - after primary, bacteria dormant, resulting in negative sputum culture but positive Mantoux, not infectious
Secondary - Immunocompromised patients maybe develop secondary when latent reactivates, infectious, occurs in lung apex, bacteria can spread locally to form a caseating granulomata or systemically (miliary)
Miliary - due to lympho-haematogenous spread to multiple organs e.g. heart, lungs, spleen, liver etc
Signs of TB
- Auscultation: often normal; crackles may be present
- Clubbing: if long-standing
Symptoms of TB
- Cough +/- haemoptysis
- Dyspnoea
- May be chest pain present
- Systemic symptoms:
- Fever
- Lethargy
- Weight loss
- Night sweats
- Lymphadenopathy
Explain Mantoux screening
- Used to look for a previous immune response to TB: indicates possible previous vaccination, latent or active TB.
- Intradermal injection tuberculin
- A type IV hypersensitivity reaction takes place
- This reaction is measured as a diameter ofindurationthat occurs across the forearm
- If positive, assess for active disease
Explain Interferon-gamma release assay (IGRA)
- Involves taking a sample of blood and mixing it with antigens from the TB bacteria. In a person that has had previous contact with TB the white blood cells have become sensitised to those antigens and will release interferon-gamma.
- More sensitive than the Mantoux test
- Used in various situations, such as:
- If the Mantoux test is positive or inconclusive
- If the Mantoux test may be falsely negative
How to investigate Active TB
-
CXR
- Primary TBmay show patchy consolidation, pleural effusions and hilar lymphadenopathy
- Latent disease may show ghon complex
- Reactivated TBmay show patchy or nodular consolidation with cavitation (gas filled spaces in the lungs) typically in the upper zones
- DisseminatedMiliary TB show “millet seeds” uniformly distributed throughout the lung fields
-
Microbiology:send three deep cough sputum samples; analyse with Ziehl-Neelsen stain (will turn red) and Mycobacterium culture
- Bronchoscopy with lavage if sputum can’t be obtained
- Lymph node aspiration for biopsy
- Nucleic-Acid Amplification Test (NAAT): rapid diagnostic test conducted on sputum or urine if specific criteria are met e.g. co-existing HIV, risk of multi-drug resistance or, aged < 15 years
- HIV and hepatitis status:assess for co-infection
Prevention of TB
BCG vaccine: intradermal injection of live attenuated (weakened) TB.
Management for latent TB
- Isoniazid andrifampicin for 3 months: to people younger than 35 years old if hepatotoxicity is a concern
OR
- Isoniazid only for 6 months: if interactions with rifampicin are a concern
- Pyridoxine (vitamin B6): usually co-prescribed with isoniazid prophylactically to help prevent peripheral neuropathy
-
Directly observed therapy:
- Offered as a three times a week dosing regimen
- Involves a key worker observing the person swallow each dose of medication
- Video observed therapy may also be an option
Side effect of Isoniazid
Peripheral neuropathy
Side effect of Rifampicin
Orange or red tears or urine
Management of Active TB
- Notification: all cases of active TB need to be notified within three working days
- Contact tracing: test contacts
- Isolate patients: negative pressure rooms are used to prevent airborne spread
- Initial phase:rifampicin, isoniazid, pyrazinamide and ethambutol (RIPE) for two months
- Continuation phase:rifampicin and isoniazid for a further four months
- Multi-drug resistant (MDR) TB: treatment will be extended for 1-24 months, with at least six drugs
- Pyridoxine (vitamin B6): usually co-prescribed with isoniazid prophylactically to help prevent peripheral neuropathy
-
Directly observed therapy:
- Offered as a three times a week dosing regimen
- Involves a key worker observing the person swallow each dose of medication
- Video observed therapy may also be an option
Complications of TB
- Empyema
- Aspergilloma
- Bronchiectasis
- Pneumothorax: TB is a cause of secondary spontaneous pneumothorax
- Miliary TB:massive lymphohaematogenous spread causing multi-organ involvement
- Extra-pulmonary disease: CNS (TB meningitis), vertebral bodies (Pott’s disease), adrenals (Addison’s disease), cervical lymph nodes (scrofuloderma), renal and GI tract
- Drug-related side effects: refer to ‘other notes’ below
Prognosis for TB
TB is a treatable condition, with a mortality rate of approximately 5%.
Without treatment, the mortality rate can be greater than 50%.
Prognosis is significantly worse for immunocompromised patients and those with extra-pulmonary disease.
How to mitigate Isoniazid side effects
Prescribe pyridoxine (Vit B6) in combination
Side effects of Pyrazinamide
Hepatitis, Gout, Arthralgia and myalgia
Side effects of Ethambutol
Optic neuritis
Define Pneumonia
Pneumonia is an acute inflammation of the terminal bronchioles and the area surrounding the alveoli.
Aetiology and types of pneumonia
-
Bacterial
- Streptococcus pneumoniae
- Haemophilus influenzae
- Staphylococcus aureus
- Klebsiella pneumonia
- Moraxella catarrhalis
- Pseudomonas aeruginosa
- Mycobacterium tuberculosis
- MRSA
- Causes of atypical pneumonia: mycoplasma pneumoniae, chlamydophila pneumoniae, legionella pneumophila, coxiella burnetti, chlamydia psittaci
-
Viral
- Respiratory syncytial virus (RSV)
- Influenza
-
Fungal
- Pneumocystic jirovicii
- Idiopathic interstitial pneumonia: group of non-infective causes e.g. cryptogenic organising pneumonia which may occur as a complication of rheumatoid arthritis or amiodarone use.
