Respiratory Flashcards
Histology of lung cancers
The histological types of lung cancer can be broadly divided into:
Small-cell lung cancer (SCLC) (around 20%)
Non-small-cell lung cancer (around 80%)
Non-small-cell lung cancer can be further divided into:
Adenocarcinoma (around 40% of total lung cancers)
Squamous cell carcinoma (around 20% of total lung cancers)
Large-cell carcinoma (around 10% of total lung cancers)
Other types (around 10% of total lung cancers)
Small-cell lung cancer cells contain neurosecretory granules that release neuroendocrine hormones. SCLC may be responsible for various paraneoplastic syndromes.
Mesothelioma is a lung malignancy affecting the mesothelial cells of the pleura. It is strongly linked to asbestos inhalation. There is a substantial latent period between exposure to asbestos and the development of mesothelioma of up to 45 years. The prognosis is very poor. Chemotherapy can improve survival, but it is essentially palliative.
Presentation of lung cancer
Shortness of breath
Cough
Haemoptysis (coughing up blood)
Finger clubbing
Recurrent pneumonia
Weight loss
Lymphadenopathy – often supraclavicular nodes are the first to be found on examination
Extrapulmonary manifestations of lung cancer
Lung cancer is associated with a lot of extrapulmonary manifestations and paraneoplastic syndromes. These are linked to different types and distributions of lung cancer. Exam questions commonly ask you to suggest the underlying cause of a paraneoplastic syndrome. Sometimes they can be the first evidence of lung cancer in an otherwise asymptomatic patient.
Recurrent laryngeal nerve palsy presents with a hoarse voice. It is caused by a tumour pressing on or affecting the recurrent laryngeal nerve as it passes through the mediastinum.
Phrenic nerve palsy, due to nerve compression, causes diaphragm weakness and presents with shortness of breath.
Superior vena cava obstruction is a complication of lung cancer. It is caused by direct tumour compression on the superior vena cava. It presents with facial swelling, difficulty breathing, and distended neck and upper chest veins. Pemberton’s sign is where raising the hands over the head causes facial congestion and cyanosis. SVC obstruction is a medical emergency.
Horner’s syndrome is a triad of partial ptosis, anhidrosis and miosis. It can be caused by a Pancoast tumour (tumour in the pulmonary apex) pressing on the sympathetic ganglion.
Syndrome of inappropriate ADH (SIADH) can be caused by ectopic ADH secreted by a small-cell lung cancer. It presents with hyponatraemia.
Cushing’s syndrome can be caused by ectopic ACTH secretion by a small-cell lung cancer.
Hypercalcaemia can be caused by ectopic parathyroid hormone secreted by squamous cell carcinoma.
Limbic encephalitis is a paraneoplastic syndrome where 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 is caused by antibodies against small-cell lung cancer cells. These antibodies also target and damage voltage-gated calcium channels sited on the presynaptic terminals in motor neurones. This leads to weakness, particularly in the proximal muscles. It can also affect the intraocular muscles, causing diplopia (double vision); levator muscles in the eyelid, causing ptosis; and pharyngeal muscles, causing slurred speech and dysphagia (difficulty swallowing). Patients may also experience dry mouth, blurred vision, impotence and dizziness due to autonomic dysfunction.
Referral criteria for lung cancer
The NICE guidelines on suspected cancer (updated December 2021) recommend offering a chest x-ray, carried out within 2 weeks, to patients over 40 with:
Clubbing
Lymphadenopathy (supraclavicular or persistent abnormal cervical nodes)
Recurrent or persistent chest infections
Raised platelet count (thrombocytosis)
Chest signs of lung cancer
TOM TIP: Remember two key examination findings that automatically indicate an urgent chest x-ray: finger clubbing and supraclavicular lymphadenopathy. These are quick things to check for. Spotting them could lead to an early diagnosis, potentially saving a patient’s life.
NICE also recommend offering a chest x-ray to patients over 40 years old who have:
Two or more unexplained symptoms in patients that have never smoked
One or more unexplained symptoms in patients that have ever smoked or had asbestos exposure
The unexplained symptoms that the NICE guidelines list are:
Cough
Shortness of breath
Chest pain
Fatigue
Weight loss
Loss of appetite
TOM TIP: It is worth noting that this is quite a vague list. It is very common for patients to present with vague symptoms of fatigue or shortness of breath, and your first thought might not be of lung cancer. If a 50 year old ex-smoker presents feeling “tired all the time” with no other symptoms, these guidelines suggest considering an urgent chest x-ray to exclude lung cancer. Equally, someone that has never smoked presenting with weight loss and general fatigue would qualify. This results in a low threshold for an urgent chest x-ray.
Investigating lung cancer
Chest x-ray is the first-line investigation in suspected lung cancer. Findings suggesting cancer include:
Hilar enlargement
Peripheral opacity (a visible lesion in the lung field)
Pleural effusion (usually unilateral in cancer)
Collapse
Staging CT scan of the chest, abdomen and pelvis is used to assess the stage, lymph node involvement and presence of metastases. This should be contrast-enhanced, using an injected contrast to give more detailed information about different tissues.
PET-CT (positron emission tomography) scans involve injecting a radioactive tracer (usually attached to glucose molecules) and taking images using a combination of a CT scanner and a gamma-ray detector to visualise how metabolically active various tissues are. They help identify metastases by highlighting areas of increased metabolic activity.
Bronchoscopy with endobronchial ultrasound (EBUS) involves endoscopy with ultrasound equipment on the end of the scope. This allows detailed assessment of the tumour and ultrasound-guided biopsy.
Histological diagnosis requires a biopsy to check the type of cells in the tumour. This can be either by bronchoscopy or percutaneous biopsy (through the skin).
Treating lung cancer
All treatments are discussed at an MDT meeting involving various consultants and specialists, such as pathologists, surgeons, oncologists and radiologists. This is to make a joint decision about the most suitable options for the individual patient.
Surgery is offered first-line in non-small-cell lung cancer to patients with disease isolated to a single area. The intention is to remove the entire tumour and cure the cancer. See below for more detail on surgery.
Radiotherapy can also be curative in non-small-cell lung cancer when diagnosed early.
Chemotherapy can be offered in addition to surgery or radiotherapy in certain patients to improve outcomes (adjuvant chemotherapy) or as palliative treatment to improve survival and quality of life in later stages of non-small-cell lung cancer (palliative chemotherapy).
Small-cell lung cancer treatment is usually with chemotherapy and radiotherapy. The prognosis is generally worse for small-cell lung cancer than non-small-cell lung cancer.
Endobronchial treatment with stents or debulking can be used as part of palliative treatment to relieve bronchial obstruction caused by lung cancer.
Lung cancer surgery
There are several options for removing a lung tumour:
Segmentectomy or wedge resection involves removing a segment or wedge of lung (a portion of one lobe)
Lobectomy involves removing the entire lung lobe containing the tumour (the most common method)
Pneumonectomy involves removing an entire lung
The types of surgery that can be used are:
Thoracotomy – open surgery with an incision and separation of the rib to access the thoracic cavity
Video-assisted thoracoscopic surgery (VATS) – minimally invasive “keyhole” surgery
Robotic surgery
Minimally invasive surgery (i.e., VATS or robotic surgery) is generally preferred as it has a faster recovery and fewer complications.
There are three main thoracotomy incisions:
Anterolateral thoracotomy with an incision around the front and side
Axillary thoracotomy with an incision in the axilla (armpit)
Posterolateral thoracotomy with an incision around the back and side (the most common approach to the thorax)
TOM TIP: A thoracotomy scar in your OSCEs indicates either a lobectomy, pneumonectomy or lung volume reduction surgery for COPD. A right-sided mini-thoracotomy incision in a cardiology station likely means minimally invasive mitral valve surgery. Absent breath sounds on an entire side indicates a pneumonectomy. Focal absent breath sounds suggest a lobectomy. Lobectomies and pneumonectomies are used to treat lung cancer. Previously, they were used to treat tuberculosis, so remember this in older patients.
Pneumonia
Pneumonia is an infection of the lung tissue, causing inflammation in the alveolar space. Pneumonia can be seen as a consolidation on a chest x-ray.
Acute bronchitis refers to infection and inflammation in the bronchi and bronchioles. Both pneumonia and acute bronchitis are classed as lower respiratory tract infections. Upper respiratory tract infections (e.g., a common cold) are usually viral. As a general rule, the lower down the respiratory tract, the higher the probability of bacterial infection, as opposed to viral.
Classification of pneumonia
Pneumonia can be classified based on where the infection was acquired:
Community-acquired pneumonia (CAP) develops in the community
Hospital-acquired pneumonia (HAP) develops after more than 48 hours in a hospital
Ventilator-acquired pneumonia (VAP) develops in intubated patients in the intensive care unit
Aspiration pneumonia is when the infection develops due to the aspiration of food or fluids, usually in patients with impaired swallowing (e.g., following a stroke or advanced dementia). Aspiration pneumonia is associated with anaerobic bacteria.
Presentation of pneumonia
Presenting symptoms of pneumonia are:
Cough
Sputum production
Shortness of breath
Fever
Feeling generally unwell
Haemoptysis (coughing up blood)
Pleuritic chest pain (sharp chest pain, worse on inspiration)
Delirium (acute confusion)
Characteristic chest signs of pneumonia include:
Bronchial breath sounds (harsh inspiratory and expiratory breath sounds) due to consolidation around the airways
Focal coarse crackles caused by air passing through sputum in the airways
Dullness to percussion due to lung tissue filled with sputum or collapsed
There may be a derangement in basic observations. These can indicate sepsis secondary to pneumonia:
Tachypnoea (raised respiratory rate)
Tachycardia (raised heart rate)
Hypoxia (low oxygen)
Hypotension (shock)
Fever
Confusion
Assessing the severity of pneumonia
The NICE guidelines on pneumonia (updated 2022) recommend using the CRB-65 scoring system out of hospital and CURB-65 in hospital. They suggest considering hospital assessment when the CRB-65 score is more than 0.
C – Confusion (new disorientation in person, place or time)
U – Urea > 7 mmol/L
R – Respiratory rate ≥ 30
B – Blood pressure < 90 systolic or ≤ 60 diastolic.
65 – Age ≥ 65
The CURB-65 score predicts mortality. NICE state 0/1 is low risk (under 3%), 2 is intermediate risk (3-15%), and 3-5 is high risk (above 15%):
Score 0/1: Consider treatment at home
Score ≥ 2: Consider hospital admission
Score ≥ 3: Consider intensive care
Causes of pneumonia
The top causes of typical bacterial pneumonia are:
Streptococcus pneumoniae (most common)
Haemophilus influenzae
Other causes include:
Moraxella catarrhalis in immunocompromised patients or those with chronic pulmonary disease
Pseudomonas aeruginosa in patients with cystic fibrosis or bronchiectasis
Staphylococcus aureus in patients with cystic fibrosis
Methicillin-resistant Staphylococcus aureus (MRSA) in hospital-acquired infections
Atypical pneumonia
Atypical pneumonia is caused by organisms that cannot be cultured in the normal way or detected using a gram stain. Treatment with penicillin is ineffective. They are treated with macrolides (e.g., clarithromycin), fluoroquinolones (e.g., levofloxacin) and tetracyclines (e.g., doxycycline).
Legionella pneumophila (Legionnaires’ disease) is typically caused by inhaling infected water from infected water systems, such as air conditioning units. It can cause a syndrome of inappropriate ADH (SIADH), resulting in hyponatraemia (low sodium). The typical exam patient has recently had a cheap hotel holiday and presents with pneumonia symptoms and hyponatraemia. A urine antigen test can be used as an initial screening test.
Mycoplasma pneumoniae causes milder pneumonia and a rash called erythema multiforme, characterised by varying-sized “target lesions” formed by pink rings with pale centres. It can cause neurological symptoms in young patients.
Chlamydophila pneumoniae causes mild to moderate chronic pneumonia and wheezing in school-age children. Be cautious, as this presentation is common without chlamydophila pneumoniae infection.
Coxiella burnetii, or Q fever, is linked to exposure to the bodily fluids of animals. The typical exam patient is a farmer with a flu-like illness.
Chlamydia psittaci is typically contracted from contact with infected birds. The typical exam patient is a parrot owner.
TOM TIP: You can remember the 5 causes of atypical pneumonia with the mnemonic: “Legions of psittaci MCQs”:
Legions – Legionella pneumophila
Psittaci – Chlamydia psittaci
M – Mycoplasma pneumoniae
C – Chlamydophila pneumoniae
Qs – Q fever (coxiella burnetii)
Other causes of pneumonia
Pneumocystis jirovecii pneumonia (PCP), a fungal pneumonia, occurs in immunocompromised patients. Patients with poorly controlled HIV and a low CD4 count are particularly at risk. It usually presents subtly with dry cough (without sputum), shortness of breath on exertion and night sweats. Co-trimoxazole (trimethoprim/sulfamethoxazole) treats PCP (brand name Septrin). Patients with a low CD4 count are prescribed prophylactic co-trimoxazole to protect against PCP.
The covid-19 virus (SARS-CoV-2) can cause pneumonia. The symptoms vary enormously. Anosmia (loss of smell) is a clue to the diagnosis. Patients may not feel particularly short of breath despite having low oxygen saturations (“silent hypoxia”). Vaccination has dramatically reduced the number of severe infections. Covid-19 pneumonia is treated with respiratory support (e.g., oxygen), dexamethasone and monoclonal antibodies.
Investigating pneumonia
Patients in the community with CRB 0 or 1 pneumonia do not necessarily need investigations.
A point-of-care test for the CRP level can be used in primary care to help guide diagnosis and the use of antibiotics.
Investigations for patients admitted to hospital include:
Chest x-ray
Full blood count (raised white cell count)
Renal profile (urea level for the CURB-65 score and acute kidney injury)
C-reactive protein (raised in inflammation and infection)
Patients with moderate or severe infection will also have:
Sputum cultures
Blood cultures
Pneumococcal and Legionella urinary antigen tests
White blood cells and CRP are raised roughly in proportion to the severity of the infection. The trend can help monitor the progress of the patient towards recovery. CRP starts rising 6 hours behind the onset of inflammation and peaks after 24-48 hours. It may initially be low before becoming very high a day or two later.
Antibiotics for pneumonia
Always follow your local area guidelines. These are developed by looking at the antibiotic resistance of the bacteria in the local area and are specific to the local population.
Mild community-acquired pneumonia is typically treated with 5 days of oral antibiotics, for example:
Amoxicillin
Doxycycline
Clarithromycin
Moderate or severe pneumonia is usually treated initially with intravenous antibiotics and stepped down to oral antibiotics as the condition improves. Respiratory support (e.g., oxygen or intubation and ventilation) is also used.
Complications of pneumonia
Sepsis
Acute respiratory distress syndrome
Pleural effusion
Empyema
Lung abscess
Death
Respiratory support
There are several options for supporting a patient’s respiratory system. These can be escalated as required. From least to most invasive, the options are:
Oxygen therapy
High-flow nasal cannula
Non-invasive ventilation
Intubation and mechanical ventilation
Extracorporeal membrane oxygenation (ECMO)
Additionally, chest physiotherapy and suction can be used to help clear secretions and improve respiratory function.
Respiratory support does not fix the underlying problem. It buys time while the underlying problem is managed.
Acute Respiratory Distress Syndrome
Acute respiratory distress syndrome occurs due to a severe inflammatory reaction in the lungs, often secondary to sepsis (e.g., pneumonia or covid-19) or trauma. There is an acute onset of:
Collapse of the alveoli and lung tissue (atelectasis)
Pulmonary oedema (not related to heart failure or fluid overload)
Decreased lung compliance (reduced lung inflation when ventilated with a given pressure)
Fibrosis of the lung tissue (typically after 10 days or more)
Clinically there is:
Acute respiratory distress
Hypoxia with an inadequate response to oxygen therapy
Bilateral infiltrates on a chest x-ray
Managing ARDS
Management of ARDS is supportive. This includes:
Respiratory support
Prone positioning (lying on their front)
Careful fluid management to avoid excess fluid collecting in the lungs
In ARDS, only a small portion of the total lung volume is aerated and has functional alveoli. The remainder of the lungs are collapsed and non-aerated. During mechanical ventilation, low volumes and pressures are used to avoid over-inflating the small functional portion of the lungs (lung protective ventilation). Positive end-expiratory pressure (PEEP) is used to prevent the lungs from collapsing further (see below for more on PEEP).
Prone positioning has several benefits:
Reducing compression of the lungs by other organs
Improving blood flow to the lungs, particularly the well-ventilated areas
Improving clearance of secretions
Improving overall oxygenation
Reducing the required assistance from mechanical ventilation
Oxygen therapy
Oxygen can be delivered by several methods. The FiO2 (concentration of oxygen) will depend on the oxygen flow rate:
Nasal cannula: 24 – 44% oxygen
Simple face mask: 40 – 60% oxygen
Venturi masks: 24 – 60% oxygen
Face mask with reservoir (non-rebreather mask): 60 – 95% oxygen
Positive End-Expiratory Pressure
Positive end-expiratory pressure (PEEP) is an important term you will likely encounter while working in a respiratory ward or intensive care.
End-expiratory pressure is the pressure that remains in the airways at the end of exhalation.
Additional pressure in the airways at the end of exhalation keeps them inflated. Respiratory support that adds positive end-expiratory pressure helps keep the airways from collapsing and improves ventilation. It reduces atelectasis, improves ventilation of the alveoli, opens more areas for gas exchange and decreases the effort of breathing.
Positive end-expiratory pressure is added by:
High-flow nasal cannula
Non-invasive ventilation (NIV)
Mechanical ventilation
High-Flow Nasal Cannula
A high-flow nasal cannula allows for controlled flow rates of up to 60 L/min of humidified and warmed oxygen.
A high flow rate reduces the amount of room air the patient inhales alongside the supplementary oxygen, increasing the concentration of oxygen inhaled with each breath.
It also adds positive end-expiratory pressure to help prevent the airways from collapsing at the end of exhalation (although this effect is reduced if the patient opens their mouth).
Finally, high oxygen flow into the airways provides dead space washout. The physiological dead space is the air that does not contribute to gas exchange because it never reaches the alveoli. Dead space air remains in the airways and oropharynx, not adding anything to respiration and collecting carbon dioxide. High-flow oxygen clears this dead space air and replaces it with oxygen, improving patient oxygenation.
Continuous Positive Airway Pressure
CPAP (continuous positive airway pressure) involves a constant pressure added to the lungs to keep the airways expanded. It is used to maintain the patient’s airways in conditions where they are likely to collapse (adding positive end-expiratory pressure), for example, in obstructive sleep apnoea.
CPAP does not technically involve “ventilation”, as it provides constant pressure and the job of ventilation is still dependent on the respiratory muscles. Therefore, CPAP is not technically classed as non-invasive ventilation (NIV).
Non-Invasive Ventilation
Non-invasive ventilation (NIV) involves using a full face mask, hood (covering the entire head) or a tight-fitting nasal mask to blow air forcefully into the lungs and ventilate them. It is not pleasant for the patient but is much less invasive than intubation and ventilation. It is a valuable middle point between basic oxygen therapy and mechanical ventilation.
BiPAP is a specific machine that provides NIV. BiPAP stands for Bilevel Positive Airway Pressure. Generally, the term NIV is used instead of BiPAP, as BiPAP refers to a specific machine rather than the therapy.
NIV involves a cycle of high and low pressure to correspond to the patient’s inspiration and expiration:
IPAP (inspiratory positive airway pressure) is the pressure during inspiration – where air is forced into the lungs
EPAP (expiratory positive airway pressure) is the pressure during expiration – stopping the airways from collapsing
Mechanical Ventilation
Mechanical ventilation is used where other forms of respiratory support (e.g., oxygen and NIV) are inadequate or contraindicated. A ventilator machine is used to move air into and out of the lungs. Patients generally require sedation whilst on a ventilator, as it can be uncomfortable and distressing. Mechanical ventilation has several adverse effects and is only used for the shortest time necessary.
An endotracheal tube (ETT) or tracheostomy is required to connect the ventilator to the lungs. There should be no leaks in the circuit. The ventilator should be able to deliver controlled pressures and volumes into the lungs.
Obstructive Lung Disease
Obstructive lung disease is diagnosed when the FEV1 is less than 70% of the FVC, meaning a FEV1:FVC ratio of less than 70%. This suggests that obstruction is slowing the air passage out of the lungs. The person may have a relatively good lung volume, but air can only move slowly in and out of the lungs due to obstruction.
In asthma, the obstruction is a narrowed airway due to bronchoconstriction. In COPD, there is chronic airway and lung damage, causing obstruction. You can test the reversibility of this obstruction by giving a bronchodilator (e.g., salbutamol). The obstructive picture is typically reversible in asthma but less so in COPD.
Restrictive Lung Disease
In restrictive lung disease:
FEV1 and FVC are equally reduced
FEV1:FVC ratio greater than 70%
Restrictive lung disease limits the ability of the lungs to expand and fill with air. The lungs are restricted from effectively expanding. This is different from obstructive lung disease, where there is obstructed airflow.
Restriction of lung expansion leads to inadequate ventilation of the alveoli and insufficient blood oxygenation.
The FEV1:FVC ratio is normal or raised in restrictive lung disease without obstructive pathology affecting airflow through the airways. The FVC is reduced due to the restriction of lung expansion and capacity.
Restrictive lung disease includes conditions that limit how well the chest wall and lungs can expand, for example:
Interstitial lung disease, such as idiopathic pulmonary fibrosis
Sarcoidosis
Obesity
Motor neurone disease
Scoliosis
TOM TIP: It is worth remembering that a low FVC indicates restrictive lung disease, and a low FEV1:FVC ratio (under 70%) indicates obstructive lung disease. A low FVC and a low FEV1:FVC ratio indicate a combination of obstructive and restrictive lung disease. This is a common data interpretation question in exams.
Asthma
Asthma is a chronic inflammatory airway disease leading to variable airway obstruction. The smooth muscle in the airways is hypersensitive and responds to stimuli by constricting and causing airflow obstruction. This bronchoconstriction is reversible with bronchodilators, such as inhaled salbutamol.
Asthma is one of several atopic conditions, including eczema, hay fever and food allergies. Patients with one of these conditions are more likely to have others. These conditions characteristically run in families.
Asthma typically presents in childhood. However, it can present at any age. Adult-onset asthma refers to asthma presenting in adulthood. Occupational asthma refers to asthma caused by environmental triggers in the workplace.
The severity of symptoms of asthma varies enormously between individuals. Acute asthma exacerbations involve rapidly worsening symptoms and can quickly become life-threatening.
Presentation of asthma
Symptoms are episodic, meaning there are periods where the symptoms are worse and better. There is diurnal variability, meaning the symptoms fluctuate at different times of the day, typically worse at night.
Typical symptoms are:
Shortness of breath
Chest tightness
Dry cough
Wheeze
Symptoms should improve with bronchodilators. No response to bronchodilators reduces the likelihood of asthma.
Patients may have a history of other atopic conditions, such as eczema, hayfever and food allergies. They often have a family history of asthma or atopy.
Examination is generally normal when the patient is well. A key finding with asthma is a widespread “polyphonic” expiratory wheeze.
TOM TIP: A localised monophonic wheeze is not asthma. The top differentials of a localised wheeze are an inhaled foreign body, tumour or a thick sticky mucus plug obstructing an airway. A chest x-ray is the next step.
Typical triggers of asthma
Certain environmental triggers can exacerbate the symptoms of asthma. These vary between individuals:
Infection
Nighttime or early morning
Exercise
Animals
Cold, damp or dusty air
Strong emotions
TOM TIP: Beta-blockers, particularly non-selective beta-blockers (e.g., propranolol), and non-steroidal anti-inflammatory drugs (e.g., ibuprofen or naproxen), can worsen asthma. These are worth remembering.
Investigating asthma
Spirometry is the test used to establish objective measures of lung function. It involves different breathing exercises into a machine that measures volumes of air and flow rates and produces a report. A FEV1:FVC ratio of less than 70% suggests obstructive pathology (e.g., asthma or COPD).
Reversibility testing involves giving a bronchodilator (e.g., salbutamol) before repeating the spirometry to see if this impacts the results. NICE says a greater than 12% increase in FEV1 on reversibility testing supports a diagnosis of asthma.
Fractional exhaled nitric oxide (FeNO) measures the concentration of nitric oxide exhaled by the patient. Nitric oxide is a marker of airway inflammation. The test involves a steady exhale for around 10 seconds into a device that measures FeNO. NICE say a level above 40 ppb is a positive test result, supporting a diagnosis. Smoking can lower the FeNO, making the results unreliable.
Peak flow variability is measured by keeping a peak flow diary with readings at least twice daily over 2 to 4 weeks. NICE says a peak flow variability of more than 20% is a positive test result, supporting a diagnosis.
Direct bronchial challenge testing is the opposite of reversibility testing. Inhaled histamine or methacholine is used to stimulate bronchoconstriction, reducing the FEV1 in patients with asthma. NICE say a PC20 (provocation concentration of methacholine causing a 20% reduction in FEV1) of 8 mg/ml or less is a positive test result.
Diagnosing asthma
The NICE guidelines (2020) recommend initial investigations in patients with suspected asthma:
Fractional exhaled nitric oxide (FeNO)
Spirometry with bronchodilator reversibility
Where there is diagnostic uncertainty after initial investigations, the next step is testing the peak flow variability.
Where there is still uncertainty, the next step is a direct bronchial challenge test with histamine or methacholine.
The BTS/SIGN guidelines (revised 2019) are similar to the NICE guidelines. They recommend categorising patients into a high, intermediate or low probability of asthma based on clinical features and investigation results, then assessing the response to treatment before making a diagnosis if there is a good response.
The Global Initiative for Asthma (GINA) guidelines (2022) are relatively similar on diagnosis, other than suggesting that FeNO testing is not useful in making or excluding a diagnosis of asthma.
Asthma pharmacology
Beta-2 adrenergic receptor agonists are bronchodilators (they open the airways). Adrenalin acts on the smooth muscle of the airways to cause relaxation. Stimulating the adrenalin receptors dilates the bronchioles and reverses the bronchoconstriction present in asthma. Short-acting beta-2 agonists (SABA), such as salbutamol, work quickly, but the effects last only a few hours. They are used as reliever or rescue medication during acute worsening of asthma symptoms. Long-acting beta-2 agonists (LABA), such as salmeterol, are slower to act but last longer.
Inhaled corticosteroids (ICS), such as beclometasone, reduce the inflammation and reactivity of the airways. These are used as maintenance or preventer medications to control symptoms long-term and are taken regularly, even when well.
Long-acting muscarinic antagonists (LAMA), such as tiotropium, work by blocking acetylcholine receptors. Acetylcholine receptors are stimulated by the parasympathetic nervous system and cause contraction of the bronchial smooth muscles. Blocking these receptors dilates the bronchioles and reverses the bronchoconstriction present in asthma.
Leukotriene receptor antagonists, such as montelukast, work by blocking the effects of leukotrienes. Leukotrienes are produced by the immune system and cause inflammation, bronchoconstriction and mucus secretion in the airways.
Theophylline works by relaxing the bronchial smooth muscle and reducing inflammation. Unfortunately, it has a narrow therapeutic window and can be toxic in excess, so monitoring plasma theophylline levels is required.
Maintenance and reliever therapy (MART) involves a combination inhaler containing an inhaled corticosteroid and a fast and long-acting beta-agonist (e.g., formoterol). This replaces all other inhalers, and the patient uses this single inhaler both regularly as a preventer and also as a reliever when they have symptoms.
Long-term management of asthma
The principles of using the stepwise ladder are to:
Start at the most appropriate step for the severity of the symptoms
Review at regular intervals based on severity (e.g., 4-8 weeks after adjusting treatment)
Add additional treatments as required to control symptoms completely
Aim to achieve no symptoms or exacerbations on the lowest dose and number of treatments
Always check inhaler technique and adherence when reviewing medications
The BTS/SIGN guidelines on asthma (2019) suggest the following steps (adding drugs at each stage):
Short-acting beta-2 agonist inhaler (e.g. salbutamol) as required
Inhaled corticosteroid (low dose) taken regularly
Long-acting beta-2 agonists (e.g., salmeterol) or maintenance and reliever therapy (MART)
Increase the inhaled corticosteroid or add a leukotriene receptor antagonist (e.g., montelukast)
Specialist management (e.g., oral corticosteroids)
The NICE guidelines on asthma (2017) suggest the following steps (adding drugs at each stage):
Short-acting beta-2 agonist inhaler (e.g. salbutamol) as required
Inhaled corticosteroid (low dose) taken regularly
Leukotriene receptor antagonist (e.g., montelukast) taken regularly
Long-acting beta-2 agonists (e.g., salmeterol) taken regularly
Consider changing to a maintenance and reliever therapy (MART) regime
Increase the inhaled corticosteroid to a moderate dose
Consider high-dose inhaled corticosteroid or additional drugs (e.g., LAMA or theophylline)
Specialist management (e.g., oral corticosteroids)
The Global Initiative for Asthma (GINA) guidelines (2022) recommend that all patients should be on an inhaled corticosteroid and should not be managed with a SABA (e.g., salbutamol) alone. The first step of their ladder is a combination inhaler containing a low-dose inhaled corticosteroid plus formoterol as required. The second step is maintenance and reliever therapy (MART) with the same inhaler. The NICE and BTS/SIGN guidelines predate the GINA guidelines and may change.
Additional management includes:
Individual written asthma self-management plan
Yearly flu jab
Yearly asthma review when stable
Regular exercise
Avoid smoking (including passive smoke)
Avoiding triggers where appropriate
Acute exacerbation of asthma
An acute exacerbation of asthma involves a rapid deterioration in symptoms. Any typical asthma triggers, such as infection, exercise or cold weather, could set off an acute exacerbation.
Presenting features of an acute exacerbation are:
Progressively shortness of breath
Use of accessory muscles
Raised respiratory rate (tachypnoea)
Symmetrical expiratory wheeze on auscultation
The chest can sound “tight” on auscultation, with reduced air entry throughout
On arterial blood gas analysis, patients initially have respiratory alkalosis, as a raised respiratory rate (tachypnoea) causes a drop in CO2. A normal pCO2 or low pO2 (hypoxia) is a concerning sign, as it means they are getting tired, indicating life-threatening asthma. Respiratory acidosis due to high pCO2 is a very bad sign.
Grading acute asthma
Moderate exacerbation features:
Peak flow 50 – 75% best or predicted
Severe exacerbation features:
Peak flow 33-50% best or predicted
Respiratory rate above 25
Heart rate above 110
Unable to complete sentences
Life-threatening exacerbation features:
Peak flow less than 33%
Oxygen saturations less than 92%
PaO2 less than 8 kPa
Becoming tired
Confusion or agitation
No wheeze or silent chest
Haemodynamic instability (shock)
The wheeze disappears when the airways are so tight that there is no air entry. This is ominously described as a silent chest and is a sign of life-threatening asthma.
Management of acute asthma
Patients with an acute exacerbation of asthma can deteriorate quickly. Acute asthma is potentially life-threatening. Treatment should be aggressive and they should be escalated early to seniors and intensive care. Treatment decisions, particularly intravenous aminophylline, salbutamol and magnesium, should involve experienced seniors.
Mild exacerbations may be treated with:
Inhaled beta-2 agonists (e.g., salbutamol) via a spacer
Quadrupled dose of their inhaled corticosteroid (for up to 2 weeks)
Oral steroids (prednisolone) if the higher ICS is inadequate
Antibiotics only if there is convincing evidence of bacterial infection
Follow-up within 48 hours
Moderate exacerbations may additionally be treated with:
Consider hospital admission
Nebulised beta-2 agonists (e.g., salbutamol)
Steroids (e.g., oral prednisolone or IV hydrocortisone)
Severe exacerbations may additionally be treated with:
Hospital admission
Oxygen to maintain sats 94-98%
Nebulised ipratropium bromide
IV magnesium sulphate
IV salbutamol
IV aminophylline
Life-threatening exacerbations may additionally be treated with:
Admission to HDU or ICU
Intubation and ventilation
The decision to intubate a patient with life-threatening asthma is generally made early as it is very difficult to intubate with severe bronchoconstriction.
Serum potassium needs monitoring with salbutamol treatment, which causes potassium to be absorbed from the blood into the cells, resulting in hypokalaemia (low potassium). Salbutamol also causes tachycardia (fast heart rate) and can cause lactic acidosis.
After an acute attack, management involves:
Optimising long-term asthma management
Individual written asthma self-management plan
Considering a rescue pack of oral steroids to start early in an exacerbation
NICE suggest referral to a specialist after 2 attacks in 12 month
COPD
Chronic obstructive pulmonary disease (COPD) involves a long-term, progressive condition involving airway obstruction, chronic bronchitis and emphysema. It is almost always the result of smoking and is largely preventable. While it is not reversible, it is treatable.
Damage to the lung tissues obstructs the flow of air through the airways. Chronic bronchitis refers to long-term symptoms of a cough and sputum production due to inflammation in the bronchi. Emphysema involves damage and dilatation of the alveolar sacs and alveoli, decreasing the surface area for gas exchange.
Unlike asthma, airway obstruction is minimally reversible with bronchodilators, such as salbutamol. Patients are susceptible to exacerbations, during which their lung function worsens. Exacerbations triggered by infection are called infective exacerbations of COPD.
Presentation of COPD
A typical presentation of COPD is a long-term smoker with persistent symptoms of:
Shortness of breath
Cough
Sputum production
Wheeze
Recurrent respiratory infections, particularly in winter
TOM TIP: COPD does NOT cause clubbing, haemoptysis (coughing up blood) or chest pain. These symptoms should be investigated for a different cause, such as lung cancer, pulmonary fibrosis or heart failure.
MRC Dyspnoea Scale
The MRC (Medical Research Council) Dyspnoea Scale is a 5-point scale for assessing breathlessness:
Grade 1: Breathless on strenuous exercise
Grade 2: Breathless on walking uphill
Grade 3: Breathlessness that slows walking on the flat
Grade 4: Breathlessness stops them from walking more than 100 meters on the flat
Grade 5: Unable to leave the house due to breathlessness
