Overview

Atypical pneumonia is an infection of the lower respiratory tract caused by different pathogens. Examples of pathogens involved in the infection are Chlamydia pneumoniae, Mycoplasma pneumoniae and Chlamydia psittaci, as well as many others.¹ This disease differs from typical pneumonias through the different pathogens that are involved, and the symptoms that they cause. Unlike the acute symptoms such as chest pain and high fever present in typical pneumonia, atypical pathogens in atypical pneumonia cause mild respiratory symptoms, headaches and gastrointestinal symptoms.²

Atypical pneumonia has a high clinical relevance in children, with atypical pathogens being highly prevalent in children and young adults, making it a common cause of mortality for the young population.^2,3

Though often mild, atypical pneumonia can lead to persistent respiratory issues in a subset of paediatric patients. These include airway dysfunctions, chronic cough and impaired lung function.

Pathophysiology in Brief

Atypical pathogens infect the organisms and lead to an intracellular infection that causes inflammation. For example, C.pneumoniae attaches to and infects lung epithelial cells (cells that form the lining of the lung walls) and enters the cells. Once inside, it modifies the host cell’s pathways, resulting in the replication of the pathogen to form new ones that then exit the cell. As a response, the body triggers the innate immune response that ultimately leads to inflammation.⁴ The innate immune system is the first line of defence in the body, protecting it from various pathogens. This immune response of the body is ultimately the cause of the immune-mediated tissue injury of the lungs.

A constant cycle of immune responses triggered by atypical pathogens leads to long-term damage. The different inflammatory responses and mediators present in the body, such as neutrophils and monocytes (types of white blood cells), secrete inflammatory cytokines, which are proteins that mediate inflammation in the body. If these cytokines persist for a longer period of time, it can lead to chronic inflammation, which is ultimately responsible for long-term damage such as bronchiectasis, chronic obstructive pulmonary disorder and impaired lung function.⁵

Common Long-Term Pulmonary Effects

Chronic cough and airway hyperreactivity

Both chronic cough and airway hyperreactivity are effects caused by atypical pneumonia, which are seen in children. In a study conducted on people affected by pneumonia or recurrent pneumonia, it was found that 92% of the children without an obvious cause demonstrated airway hyperreactivity.⁶ This causes the lungs to react to stimuli more than they normally would, leading to coughing and wheezing.

Persistent cough is a symptom that can interfere with children’s day-to-day lives. When conducting studies on children affected by pneumonia, one-third of the children still presented coughing after 4 weeks. By 6 months, this number dropped to one quarter.⁷ Although often resolving by itself, treating persistent coughs may require bronchodilator therapy (medications that help the branches of the lungs relax). This has seen some improvement in children’s symptoms.⁶

Asthma-like symptoms or asthma development

Atypical pneumonia may contribute to the development of asthma or can cause symptoms that are similar to those seen in people suffering with the disease. After a study was conducted on children admitted to hospital for pneumonia treatment, it was found that 45% of them had developed asthma 7.4 years after being treated for pneumonia.⁸ Mycoplasma pneumoniae is one such atypical pathogen involved in the development of atypical pneumonia and can also cause an onset of asthma and exacerbations. The pathogen is detected in the lower lung airways of people suffering from asthma more frequently when comparing them with patients who do not suffer from asthma. This was further confirmed when people suffering from asthma were treated with an antibiotic working specifically against Mycoplasma pneumoniae and showed an improvement in lung function.⁹

But how exactly do Mycoplasma pneumoniae and other atypical pathogens cause asthma–like symptoms? The answer is not very simple, but it is, once again, linked to the interactions between the pathogen and the immune response against it. Atypical pathogens stimulate the immune response and cause the production of cytokines and other immune cells. Physiological changes that occur in the body include bronchial obstruction (blockages of the branches of the lungs) and the thickening of cell walls.⁹ Both of these changes contribute to the symptoms of asthma.

One other factor that contributes to asthma-like symptoms in children caused by atypical pneumonia is airway remodelling. This refers to the structural changes in the walls of the airways from chronic inflammation. This is seen when studying the effects of atypical pathogens like Chlamydia pneumoniae and the damage caused to the airways. Airway remodelling as a result of the chronic inflammation caused by the pathogen leads to the thickening of the cell walls and membranes, as well as other, more complicated mechanisms that cause asthma-like symptoms.¹⁰

Bronchiectasis 

Although rarer and present only in severe cases, bronchiectasis is one of the long-term effects in children suffering from atypical pneumonia. It is the irreversible widening of bronchi along with the destruction of bronchial walls, inflammation and bacterial infection. It often causes persistent coughing and the production of sputum.¹¹ Similarly to the other long-term effects, bronchiectasis is triggered by an infection that leads to an immune response primarily driven by neutrophils. The persistent recruitment of these cells to the sites of infection causes damage to the airways. The associated damages from airway destruction are the dilation of the bronchi, the thickening of the walls of the bronchi or the plugging of the mucus. The abnormal clearance of the mucus in the airways further leads to lung damage and remodelling of the airways. This trapped mucus can’t effectively be cleared from the airways and is associated with bronchiectasis.¹²

As previously mentioned, this complication, as a result of atypical pneumonia in children, is only present in rarer cases. With appropriate and early treatment, this bronchiectasis can be reversed and treated in children.

Impaired lung function

Pneumonia in childhood can cause a longer-term effect of impaired lung function, which can affect growth and exercise tolerance. After conducting follow-up studies on people who have been affected with pneumonia in the first three years of their childhood, they were shown to have a decreased FEV1. The follow-up studies were conducted on the patients at ages 11, 16 and 22 and compared their FEV1 to people of the same age who had not suffered from pneumonia during childhood. As expected, the young adults who had suffered from pneumonia in their first three years of childhood had a significantly lower FEV1.¹³ Although, as a result of atypical pneumonia, this long-term effect is milder compared to the previous ones in this list.

Risk Factors for Long-Term Sequelae

Delayed or inadequate treatment of atypical pneumonia in children can be very dangerous, as it can be a factor which causes longer-term effects and sequelae. Host vulnerability between children is also a factor that plays a role. Whether children affected by pneumonia have asthma, prematurity or immunodeficiency changes their predisposition to developing long-term sequelae. For example, primary immunodeficiencies in children are an accelerator of lung injury and predispose children to lung changes that can increase their risk factors for long-term sequelae.¹⁴ As previously discussed as well, asthma and atypical pneumonia go hand in hand together and asthma can be an underlying cause of atypical pneumonia and vice versa. 

Environmental factors such as tobacco smoke exposure or pollution can affect children and increase their risk of developing lung complications. Studies have found that a number of respiratory diseases, including pneumonia, have been linked with environmental risk factors, particularly in children from lower socioeconomic backgrounds. Along with pollution and tobacco smoke exposure, coal dust, nitrogen and sulphur dioxides were also associated with these respiratory diseases.¹⁵

Monitoring and Management

We have talked about the risk of long-term effects and how these may impact children’s lives, but how can we prevent these and when should parents start suspecting long-term issues? Typically, if the symptoms of atypical pneumonia persist in children for over 4 weeks, then additional concern should be raised regarding long-term sequelae.¹⁶ As a follow-up, children may need to be evaluated for risk prevention through a referral to a pulmonologist (lung specialist) and for chest X-rays or spirometry.

Management of the long-term effects of atypical pneumonia can be different depending on the symptoms shown. As previously discussed, when children present asthma-like symptoms, the treatment options tend to be inhaled therapies such as bronchodilators or inhaled corticosteroids. Airway clearance techniques can also be a treatment option for young adults and children as a way to help clear airway obstruction and improve lung function, which is very helpful, especially for bronchiectasis complications.¹⁷ Additional pathogen infection therapies may include vaccinations.

Summary

Although it may sometimes seem that atypical pneumonia is a mild disease that just comes and goes, it is important to understand that it can have lasting pulmonary effects, especially in vulnerable children. Although the different risk factors present make the longer-lasting effects different from child to child, early detection is important to ensure that children can overcome the disease swiftly and prevent the development of further complications. With proper treatment given to children, depending on the types of different long-term symptoms that they present, children can recover fully.