Research involving patients at CUH with severe pneumonia has revealed the condition has three ‘pneumotypes’. In future, understanding which type a patient has could be life-saving, helping the right patients to get the right treatments sooner.
Patients with severe pneumonia require urgent specialist care and are generally treated in intensive care units (ICUs). While some patients respond well to treatment and recover quickly, for others the condition rapidly becomes life-threatening. This discovery helps to explain why.
Even though we’re able to treat the initial infection, many patients with severe pneumonia still struggle to come off the ventilator and can develop lung failure. Therapies to tackle inflammation in the lungs have had mixed results in clinical trials – some suggest they are beneficial, others that they're harmful.
Dr Andrew Conway Morris from the Department of Medicine at the University of Cambridge and an ICU consultant at Addenbrooke’s Hospital
Treatments that work well for some subtypes may not work for others, and could even make them worse. The researchers hope that better understanding of each subtype will lead to better treatments and help appropriate treatments to be chosen for each patient.
Currently, doctors look at symptoms, imaging and blood tests to diagnose severe pneumonia. Symptoms typically include fever or hypothermia, low oxygen levels, breathing difficulties and confusion.
In the study, published today in Nature Communications, the researchers collected fluid from the lung to study immune cells, inflammatory signals, and gene activity. This allowed them to discover the three different subtypes, which they call ‘pneumotypes’:
- About half of patients (49%) had a suppressed immune system and damage to the lining of their lungs. These patients didn’t have much inflammation, which may explain why treatments targeting inflammation fail for some patients.
- Around one in four (23%) of patients had balanced immune activity and signs of healing in their lungs. These patients often recovered faster despite initially appearing as severely ill as other patients.
- The final group required the greatest support and took longer to recover. They had high levels of inflammation in their lungs and are the patients most likely to benefit from anti-inflammatory treatments.
If we know which subtype of pneumonia an individual has, we can potentially tailor their treatment more precisely, boosting the immune response in some, while calming harmful inflammation in others. This has the potential to help critically ill patients, reduce deaths from pneumonia, shorten ICU stays and cut unnecessary antibiotic use.
Dr Vilas Navapurkar from the John Farman Intensive Care Unit at Addenbrooke’s Hospital
At the moment, the tests the researchers used to identify each subtype are too complex and slow to be used in clinical care but the researchers hope to develop simplified tools that could help treat patients in future.
Even though on the surface, all of the patients seemed to have similar types of pneumonia, with comparable illness severity, oxygen levels and clinical diagnoses, their outcomes were very different.
It was only when we drilled down and looked at patterns of inflammation that the differences became apparent. Severe pneumonia is not a single disease, but several biologically distinct conditions that happen to look alike. This helps explain why ‘one-size-fits-all’ treatments – including some immune-modulating drugs – have often failed in clinical trials.
Dr Mark Jeffrey from the Department of Medicine at the University of Cambridge, the study’s first author
Pneumonia is the commonest infectious cause of death worldwide, responsible for an estimated 2.5 million deaths per year. In severe cases, patients may need to be admitted to an ICU and given mechanical ventilation. Severe pneumonia accounts for six in 10 infections managed in intensive care, and spread of the infection within ICUs is a significant concern.
The study was funded by Addenbrooke’s Charitable Trust (opens in a new tab), the National Institute for Health and Care Research Cambridge Biomedical Research Centre, and The Forster Foundation.