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This article focuses on two chronic lung conditions, bronchiectasis and cystic fibrosis. These conditions are linked, because the genetic condition cystic fibrosis can commonly lead to bronchiectasis. However, it is important to understand the differences between these conditions.
Bronchiectasis is a lung condition characterised by the chronic dilation of one or more bronchi. These bronchi exhibit poor mucus clearance, and people with bronchiectasis are therefore predisposed to recurrent or chronic bacterial infection.
Diagram - The difference between healthy bronchi and bronchi found in patients with bronchiectasis
Public Domain Source by National Heart Lung and Blood Institute [Public domain]
Common infectious organisms include Haemophilus influenzae (the most frequent, found in about 20 to 40% of people in UK studies) and Pseudomonas aeruginosa (about 10 to 30%). Others include Moraxella catarrhalis, Streptococcus pneumoniae, Staphylococcus aureus and the Enterobacteriaceae (a family of gut bacteria). Non-tuberculous mycobacteria (NTM, environmental relatives of the bacteria that cause tuberculosis) are found in only about 1 to 10% of people. The mould Aspergillus may also be grown from sputum (mucus coughed up from the lungs), particularly in people with asthma or allergic bronchopulmonary aspergillosis (see below). Most of the causes of bronchiectasis below damage the airways or their defences, which lets these organisms take hold.
There are many different causes of bronchiectasis, although in many patients no obvious cause can be found:
- Post-infection - damage to the airways after a severe or recurrent lower respiratory tract infection, such as pneumonia, whooping cough or tuberculosis.
- Immunodeficiencies - such as hypogammaglobulinaemia (a condition characterised by low levels of immunoglobulin G, or IgG, an antibody), or secondary immunodeficiency (such as HIV infection).
- Mucociliary Clearance Defects - conditions in which mucus is not moved out of the airways properly, such as cystic fibrosis or primary ciliary dyskinesia (PCD, in which the cilia, the tiny hairs lining the airways, do not beat effectively).
- Obstruction - by things such as a foreign body, a tumour or an enlarged lymph node pressing on the airway from outside.
- Toxic Insult - aspiration (breathing in) of acidic gastric (stomach) contents, or occupational smoke inhalation (breathing in smoke at work).
- Allergic Bronchopulmonary Aspergillosis - a mixed type I (IgE-mediated) and type III (IgG-mediated) hypersensitivity reaction (an exaggerated immune response) that occurs when spores of the mould Aspergillus are breathed in. It is seen mainly in people with asthma or cystic fibrosis. Classically, it causes bronchiectasis of the central (proximal) airways, with normal peripheral airways, although the periphery is sometimes involved too.
- Autoimmune Disease - such as rheumatoid arthritis or Sjogren’s Syndrome (an autoimmune condition that causes dry eyes and a dry mouth).
Tobacco smoking is not established as an independent direct cause of bronchiectasis in the same way as recognised causes such as cystic fibrosis or previous severe infection. However, Yang et al. (2022), PMID 35629114 reported an association between smoking and newly diagnosed (incident) bronchiectasis. This observational study followed more than 6.8 million Korean adults aged 20 to 39 years. An association does not prove that smoking causes bronchiectasis, but it does not rule out a risk either. Smoking cessation remains appropriate advice: NICE NG209 recommends advising people who smoke to stop and explaining how stop-smoking support can help.
The most common symptoms of bronchiectasis include:
- Chronic cough
- Daily sputum (mucus coughed up from the lungs) production which can vary in quantity, consistency, and colour
- Breathlessness on exertion
- Intermittent haemoptysis (coughing up blood) commonly presenting as red streaks in the sputum
- Chest pain
- Fatigue
- Patients may also experience a wheeze, but this is less common
Bronchiectasis makes up one part of the triad (a group of three features) of classical features in two conditions. These are important differential diagnoses to consider when taking a history from a patient with suspected bronchiectasis.
- Young’s Syndrome - a triad of bronchiectasis, chronic sinusitis (long-lasting inflammation of the sinuses, the air-filled spaces in the face) and obstructive azoospermia in males. In obstructive azoospermia, sperm are made normally but are blocked from reaching the semen, so the man is infertile. The underlying cause is not well defined. One suggestion is that abnormally thick mucus builds up in the lungs and sinuses (stasis, meaning it is not cleared away) and blocks the passage of sperm through the epididymis (the coiled tube beside each testis where sperm mature), but this is not proven.
- Kartagener’s Syndrome - a triad of bronchiectasis, chronic sinusitis and situs inversus. This condition is the form of Primary Ciliary Dyskinesia (PCD) that includes situs inversus. In PCD, the cilia (the tiny hairs that move mucus along the airways) do not move as effectively as they should. Situs inversus (where the organs are arranged as a mirror image of normal) occurs in about 50% of patients with PCD, so Kartagener’s Syndrome describes about half of all people with PCD.
The investigation of suspected bronchiectasis has two parts: imaging to confirm the diagnosis, and other tests to look for a cause and for infection. Sputum is cultured, including for mycobacteria (the bacteria that cause tuberculosis and related infections). Blood tests measure immunoglobulins (antibodies) to look for immunodeficiency, and test for allergy to Aspergillus. Tests for cystic fibrosis and primary ciliary dyskinesia are added when the history points to them.
The gold standard imaging investigation for bronchiectasis is a high-resolution CT scan (HRCT), which takes thin slices through the chest to show the airways in detail. In the appropriate clinical context, it shows bronchial dilation, where the bronchus is wider than the adjacent blood vessel, and bronchial wall thickening. Classically, it also shows the ‘Signet Ring sign’. This describes a very dilated bronchus lying close to its smaller pulmonary artery, so that the pair look like a signet ring. On the image below, it can be seen in the right middle and lower lobes.
Image - CT scan of a patient with bronchiectasis. It shows widened airways, some of which are indicated by arrows. It also shows the ‘signet ring sign’ with white pulmonary arteries beside dark, dilated bronchi
Creative commons source by Mcgfowler [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)]
Management of bronchiectasis that is not due to cystic fibrosis (the focus of the British Thoracic Society, or BTS, guideline) involves treating any underlying cause. People are taught airway clearance techniques by a respiratory physiotherapist to help them clear mucus. Humidification (breathing in a mist of sterile water or normal saline, a salt solution) can be considered to help clear mucus, and a trial of mucoactive treatment (a medicine that makes mucus easier to cough up) can be considered if sputum is hard to cough up. Recombinant human DNase (dornase alfa), the first choice in cystic fibrosis, is not used routinely. Sputum samples are sent routinely, and each person has a management plan for infective exacerbations (flare-ups, described below). Annual influenza (flu) vaccination and pneumococcal vaccination are offered to everyone with bronchiectasis.
Long-term antibiotics can be considered in selected patients, particularly those with frequent exacerbations or regular isolation of Pseudomonas aeruginosa or MRSA in sputum, under specialist respiratory guidance. Inhaled corticosteroids (steroid inhalers) are not routinely offered unless the person has another reason to use them, such as asthma or COPD (chronic obstructive pulmonary disease). A trial of a long-acting bronchodilator (an inhaler that widens the airways) can be offered to people with significant breathlessness.
Pulmonary rehabilitation (a supervised programme of exercise and education) should be offered to people who are limited by breathlessness. The BTS defines this as a score of 1 or more on the Modified Medical Research Council (mMRC) dyspnoea scale, which grades how much breathlessness limits everyday activity. It aims to increase exercise tolerance.
An exacerbation (flare-up) of bronchiectasis is defined by a deterioration in three or more key symptoms for at least 48 hours, together with a clinician deciding that the bronchiectasis treatment needs to change. The key symptoms are cough; sputum volume and/or consistency; sputum purulence (pus in the sputum); breathlessness and/or exercise tolerance; fatigue and/or malaise (feeling generally unwell); and haemoptysis.
Treatments for exacerbations include aerosolised or oral antibiotics, and supportive care like IV fluids if necessary.
Cystic fibrosis (CF) is an autosomal recessive disease (two faulty copies of the gene are needed, one from each parent). It is caused by a mutation in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, which lies in the long arm of chromosome 7. The faulty gene makes a CFTR protein that moves chloride poorly across cell surfaces. As a result, the cells that line the airways, pancreas and other organs make thick, dehydrated body fluids. This causes multisystem disease, mainly in the respiratory and gastrointestinal systems.
Cystic fibrosis affects more than 11,000 people in the UK (source).
A person with cystic fibrosis will usually present in one of the following ways:
One or more characteristic phenotypic features (the signs and symptoms that can be observed) of the disease. About 1 in 7 newborn babies with cystic fibrosis have meconium ileus, in which the bowel is blocked with sticky secretions. This causes signs of obstruction soon after birth: vomiting, abdominal distension and delay in passing meconium (the first stool passed by a baby). Exocrine pancreatic insufficiency (the pancreas does not release enough digestive enzymes) is common in CF and can cause intestinal malabsorption (poor absorption of food), often apparent in infancy. Thick secretions obstruct pancreatic ducts, reducing the delivery of digestive enzymes to the intestine. Some people with CF retain pancreatic function, so malabsorption should be assessed rather than assumed. Other characteristics are recurrent chest infections, or infertility in males. Most people are now diagnosed in infancy, but some are first diagnosed later, including in adulthood. NICE advises assessing adults for CF (with a gene test) when they have, for example, bronchiectasis, pancreatitis or obstructive azoospermia (sperm are made but are blocked from reaching the semen).
A positive newborn screen identifies a baby who needs further assessment; it is not itself a diagnosis. In the UK, the initial heel-prick blood-spot test measures immunoreactive trypsinogen (IRT), a protein made by the pancreas that is often raised in babies with CF. Depending on the result, the screening pathway uses CFTR DNA testing and sometimes a repeat IRT measurement. Babies with a suspected positive result are referred for diagnostic assessment, including sweat testing. A family history may warrant assessment even when screening is negative.
In a person with symptoms suggestive of cystic fibrosis, a quantitative sweat chloride test is a key diagnostic investigation. A concentration ≥60 mmol/L supports the diagnosis. The result should be confirmed on a separate occasion or with an independent diagnostic method, and interpreted alongside the clinical picture and CFTR testing. A result of 30–59 mmol/L is intermediate and needs further assessment. A result below 30 mmol/L is normal, but it does not exclude every case of CF.
Common complications of cystic fibrosis include:
Persistent respiratory infections needing aggressive treatment with physiotherapy and antibiotics. This occurs because the mucus in the lungs of these patients is very viscous, meaning it is hard to cough up. This stasis (build-up) of mucus makes the lungs more prone to infection. Some people also take antibiotics to prevent infection (prophylactic antibiotics). For example, NICE advises flucloxacillin for children with CF from diagnosis up to age 3, and to consider continuing it up to age 6, to protect against Staphylococcus aureus infection.
Low body weight or restricted growth in children due to malabsorption from the gastrointestinal tract. This is managed with input from a specialist dietitian and, in people with exocrine pancreatic insufficiency, pancreatic enzyme replacement capsules taken with food. If malnutrition persists, tube feeding may be needed. This can be through an NG (naso-gastric) tube, which is passed through the nose into the stomach, or a PEG (percutaneous endoscopic gastrostomy), which is a tube placed directly into the stomach through the skin of the abdomen.
Cystic fibrosis-related diabetes develops when pancreatic disease impairs the function of insulin-producing beta cells, leading to insufficient insulin secretion. Pancreatic scarring and disturbances in beta-cell function contribute to this endocrine problem. Insulin resistance can also contribute, particularly during infection or corticosteroid treatment.
Distal intestinal obstruction syndrome, in which there is a build-up of thickened faeces in the bowel, presenting with a palpable mass in the right iliac fossa (the lower right part of the abdomen).
Further complications are outlined below, grouped by body system. Many arise because thick secretions block the airways, ducts and glands.
- Lungs - bronchiectasis, pneumothorax (air leaking into the space around the lung, which can make the lung collapse), haemoptysis, respiratory failure and allergic bronchopulmonary aspergillosis.
- Upper Respiratory Tract - chronic sinusitis.
- Gastrointestinal System - oesophageal reflux and oesophagitis.
- Hepatobiliary System (the liver and bile ducts) - chronic liver disease, portal hypertension (raised pressure in the veins that carry blood from the gut to the liver) and gallstones.
- Cardiac System - right-sided heart failure (cor pulmonale, strain on the right side of the heart caused by severe lung disease).
- Musculoskeletal System - arthritis and osteoporosis.
- Reproductive Tract - male infertility due to absence of the vas deferens (the tubes that carry sperm from the testes).
The management of cystic fibrosis is complicated and is led by a cystic fibrosis specialist centre with a multi-disciplinary team. The care is holistic, but mainly focuses on maintaining lung health and nutritional status. Co-morbidities (other conditions that occur alongside CF, such as CF-related diabetes) will also be managed. Treatment can include prophylactic antibiotics (antibiotics given to prevent infection) for some people, and physiotherapy to encourage mucus clearance. Mucoactive agents are medicines, usually breathed in through a nebuliser (a device that turns liquid medicine into a mist), that make mucus easier to clear from the lungs. NICE advises dornase alfa as the first choice, with hypertonic saline (a stronger salt solution) added, or used alone, if the response is inadequate. Many people with CF now also take a CFTR modulator, a medicine taken by mouth that helps the faulty CFTR protein to work better. NICE recommends several CFTR modulators for people with certain CFTR variants, depending on their age.
There is a range of lifestyle advice that can be given to a person with cystic fibrosis:
- Do not smoke.
- Avoid other patients with cystic fibrosis to reduce the risk of cross-infection.
- Avoid other people who have an infection, for example do not visit friends if they have a cold.
- Avoid jacuzzies as they are a known source of Pseudomonas infection.
- Avoid farms as they are a known source of Aspergillus infection.
- Have the flu jab and all other scheduled vaccinations.
Patients with CF who want to start a family should also be referred for pre-conceptual counselling. Because CF is an autosomal recessive disease, the patient suffering from CF will have two copies of the faulty gene. This means that they will pass one copy on to all of their children. If the partner has no copies of the faulty gene, the children will not have the disease but will all be carriers (people with one faulty copy, who usually have no symptoms). The partner can have a carrier test, but the test looks only for the commonest faulty variants. A negative result therefore lowers the chance that the partner is a carrier without removing it completely.
Edited by: Dr. Maddie Swannack
Reviewed by: Dr. Thomas Burnell and Dr. Marcus Judge
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