What is croup?

Croup is a condition characterised by excessive, harsh coughing which sounds like barking. It can be caused by many viruses, but most commonly by parainfluenza viruses. Other culprits of croup include adenoviruses, influenza viruses and respiratory syncytial viruses. Children are most commonly affected, though paediatric cases up to the age of 15 have been seen. Adults are rarely affected, and when they are, the symptoms are less severe. Typically, the larynx (voice box) is affected, especially the area right underneath the vocal cords called the subglottis, which can cause respiratory symptoms. The trachea (windpipe) can also be affected, causing breathing difficulties. Less commonly, the bronchi (airways) may be affected.¹ 

Symptoms of croup include:

• Barking sound when the child coughs
• Harsh, high-pitched sound when the child breathes in, called stridor
• Fever
• Sore throat

How can croup be treated?

Though normally mild, sometimes the croup can become severe and require medical attention. Home remedies include paracetamol to ease pain or fever, rest and hydration. Inhaling humidified air can help improve inflammation, easing symptoms and aiding recovery. This can be achieved by adding a humidifier to the patient’s room or sitting in the bathroom after a shower and inhaling the air there for some time. 

If this does not alleviate symptoms and degression occurs, medical attention may be required (normally in less than 5% of cases).¹ Oral or injected corticosteroids may be given to reduce inflammation. Alternatively, vaporised adrenaline may be given via a nebuliser to cause the bronchi to relax, opening up the airways to allow the patient to breathe more easily.¹ It can reduce airway oedema and mucous secretion to ease breathing and alleviate symptoms. 

What is a parainfluenza virus?

Parainfluenza viruses are a specific family of viruses that attach to mucous membranes and use this avenue to cause infection, especially in children. Sneezes and coughs can also allow the virus to spread, enabling it to infect others who come into contact with the infected drops. The virus typically will incubate within an infected host for 2-6 days before symptoms may be observed.

There are four types of human parainfluenza virus, with type 1 and 2 most commonly responsible for croup whereas type 3 is often the cause of respiratory illnesses like bronchitis. Type 4 normally causes mild illness, not being a serious cause for concern. 

Type 1 and 2 can also cause upper and lower respiratory tract infections like pneumonia or bronchiolitis, so if concerned, medical help should always be sought. 

How does the immune system typically respond to viruses?

The body has natural barriers, like the skin, which can prevent germs, like viruses, from entering the body. Openings, such as the nose, produce mucous, which can trap entering pathogens to prevent them from multiplying. Other defences include resident ‘good’ bacteria which live in the body, making it difficult for harmful pathogens to live there.² 

Once the virus evades the body’s natural defences, it enters the patient’s cells as viruses cannot survive long without a host. They use the nucleus of the patient’s cells to make new virus parts, then package the viral parts into new viruses. The patient’s body is used as a factory to create many new copies of the virus. When lots of copies have been made, they burst out of the cells they inhabit and into new ones, therefore causing damage and death to the cells they just left. The damaged and dying cells release factors into the bloodstream as they die, alerting the patient’s body about the infection. 

Immune cells like macrophages, dendritic cells, T-helper cells and epithelial cells, present in the blood vessels, can recognise the damaged patient’s cells. Once they have recognised the virus, these immune cells release inflammatory factors.²

These factors cause the blood vessels to dilate and become more permeable, so more immune cells can rush to the site of infection and leave the blood vessels easily to attack and engulf the virus in the infected cells.⁴ Immune cells that follow the inflammatory factors to the site of infection include neutrophils, monocytes and lymphocytes. They help clear viral proteins, viruses and damaged cell parts.^2,5 Mast cells (immune cells which normally live in the tissue and not in the bloodstream) are also activated by the release of these inflammatory factors and aid in attacking the virus and amplifying the release of the inflammatory factors to increase the immune response.⁶ 

The increased permeability of blood vessels makes it easier for immune cells to leave the bloodstream and enter the tissues, increasing the fluid entering the tissues to allow this voyage.² Proteins and other factors may flow out of the bloodstream during this time. Excessive inflammation can lead to swelling of the tissues surrounding the infection, such as the trachea and larynx, called oedema. Its persistence may lead to these narrow tubes becoming even narrower, so it is harder to breathe and speak, causing the common symptoms of respiratory illnesses, like croup. Various immune cells release other factors (pyrogens) that cause fever over time, which allows the immune system to work better at a more optimal temperature.⁷ 

How does croup’s effect on the immune system differ from other respiratory illnesses?

Reportedly, croup leads to higher parainfluenza-specific antibodies normally observed in allergic reactions, such as asthma. This is uncommon in other respiratory illnesses and may lead to greater mast cell activation. 

Greater proliferation of lymphocytes, such as T cells, also happens with parainfluenza virus infection, suggesting an over-emphasised response that could be responsible for the severity of the symptoms. This is not normally seen in other respiratory illnesses and may be why croup causes oedema more frequently than the flu. 

Regulatory T cells, which help control inflammatory activation by inhibiting over-activation of lymphocytes, may be dysregulated as histamine-induced repression of T and B cells was decreased, leading to over-activation of the immune system in croup patients.⁸ 

All these factors may play a role in croup’s pathogenesis, leading to worse symptoms from greater inflammation. This process can damage the uninfected tissue as the body tries to fight off infection. 

Differences in early infants

Newborns are at greater risk of developing croup, with those around 3 months old more likely to develop severe symptoms and require medical attention. This is because of how the immune system develops. 

During pregnancy, maternal antibodies are transported to the foetus During birth, the baby is exposed to the bacteria in the vaginal canal that prompts the early base layer of the innate immune system from the gut microbiome population. Children born via a caesarean section (c-section) do not experience this and thus, may have a slightly different immune system for the first few months of life, although they will have neutrophils and macrophages from hematopoietic stem cells.^9,10 

Breastfed children receive passive immunity from the mother as maternal antibodies and other compounds pass through the colostrum in the breast milk. Breastfeeding also helps to increase the number of healthy bacteria in the infant’s gut, which can influence the immune system.^11,12 Moreover, breast milk contains anti-inflammatory factors that can prevent over-activation of the immune system, for example in allergies or autoimmune diseases.¹³ 

As some children are fed instant formula milk instead of breastmilk, they do not have the same gut microbiome, nor the passive immunity from maternal antibodies. Formula milk does provide nourishment for the immune system in the form of active compounds, but they may differ from the immune-rich compounds in breast milk and the immune system may develop slightly differently.^12,13 These factors can result in greater susceptibility to croup, leading to more severe symptoms if caught. 

Infants below 6 months old only have a general immune system and cannot make their own antibodies yet.¹⁴ Therefore, their response to infection from the parainfluenza virus can be severe, especially if they haven’t been breastfed, and vaccines for croup don’t exist.¹⁴ Should children in this age group develop a fever beyond 38 degrees, medical attention should be sought.

Summary

Croup is a common infectious disease among children, most likely caused by parainfluenza viruses type 1 or 2. It can be serious in younger infants due to how their immune system develops. Several factors can affect the immune response to croup, such as the way children are born, genetics, and whether they are breastfed. In most cases, the disease can resolve on its own, but medical attention is required in severe cases.