Cambridge researchers have shown that there are three different subtypes of severe pneumonia, helping to explain why some patients in intensive care units (ICUs) recover from the disease faster than others, while for others the disease can be life-threatening.
Their findings could help inform personalized treatments in the future, ensuring each patient receives the most appropriate treatment.
Pneumonia is the most common infectious cause of death worldwide, killing an estimated 2.5 million people annually. In severe cases, patients may be admitted to the ICU and require a ventilator. Six out of 10 infections managed in intensive care units are severe pneumonia, and the spread of infection within the ICU is a serious concern.
Doctors have long struggled to understand why patients whose symptoms appear clinically similar have vastly different recoveries. Some people respond quickly to treatment, but others remain seriously ill for several weeks or die.
Even if the initial infection can be treated, many patients with severe pneumonia still struggle to be taken off ventilators and can develop lung failure. Treatments that address lung inflammation have had mixed results in clinical trials, with some saying they are beneficial and others saying they are harmful.
The current approach of classifying patients by clinical syndromes such as sepsis and acute respiratory distress syndrome without considering the underlying biology risks missing what is important. Instead of asking, “Does this patient have pneumonia?” you should ask, “What is the pattern of inflammation in this patient’s lungs?” ”
Dr Andrew Conway-Morris, ICU Consultant, University of Cambridge Medical School, Addenbrookes Hospital, Cambridge
According to the survey results announced today, nature communicationsProfessor Conway Morris and team recruited patients admitted to the ICU at Addenbrookes Hospital, part of Cambridge University Hospitals NHS Foundation Trust, with suspected severe pneumonia.
Severe pneumonia is usually diagnosed by a combination of symptoms, imaging tests, and blood tests. Symptoms usually include fever or hypothermia, low oxygen levels, difficulty breathing, and confusion.
But rather than relying solely on blood tests and scans, the Cambridge team analyzed immune cells, inflammatory signals and gene activity in fluid taken from patients’ lungs. They discovered that there are three different biological types (“pneumonia types”) of severe pneumonia, none of which can be reliably detected by standard blood tests, although they are strongly correlated with how patients recover.
The most common type of pneumonia, accounting for nearly half (49%) of cases, was characterized by immunosuppression, severe damage to the lining of the lungs, and bleeding in the alveoli (small air sacs within the lungs). There were fewer signs of inflammation, which may explain why treatments targeting inflammation can fail or harm some patients.
The second pneumonia type, which accounted for just under a quarter (23%) of cases, was characterized by a balanced immune response and active repair of damage to the lungs. Patients are most likely to recover faster from this pneumonia type and spend the least amount of time on a ventilator, even if they initially appear as ill as others.
Patients with the most dangerous type of pneumonia (most similar to “classic” pneumonia) were on ventilators the longest and had severe symptoms for a longer period of time. They had severe and persistent inflammation, and their lungs had large numbers of immature immune cells. This group is most likely to respond to anti-inflammatory therapy, the researchers said.
The study’s lead author, Dr Mark Jeffrey from the University of Cambridge Medical School, said: ‘Although on the surface it appeared that all the patients had similar types of pneumonia and had similar severity, oxygen levels and clinical diagnoses, the outcomes were very different.
“It was only when we dug deeper into the patterns of inflammation that the differences became apparent. Severe pneumonia is not a single disease, but several biologically distinct conditions that happen to be similar. This helps explain why ‘one-size-fits-all’ treatments, including some immunomodulatory drugs, often fail in clinical trials.”
The tests used to determine lung type are too complex for rapid classification, but researchers hope to develop a simplified tool that can stratify patients and ultimately provide tailored treatment.
Dr Vilas Navapurkar, from Addenbrooke’s Hospital’s John Furman Intensive Care Unit, said: “Knowing which subtype of pneumonia an individual has may allow us to tailor patient treatment more precisely, increasing the immune response in some patients and quelling harmful inflammation in others. This could help critically ill patients, reduce deaths from pneumonia, shorten ICU stays and cut down on unnecessary antibiotic use.”
This research was funded by the Addenbrooke’s Charitable Trust, the National Institute for Health and Care Excellence Cambridge Biomedical Research Center and the Forster Foundation. Professor Conway Morris is a Fellow of Emmanuel College, Cambridge.
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Reference magazines:
Jeffrey, M. others. (2026). Pulmonary inflammation in severe pneumonia is characterized by compartmentalized and mechanistically distinct subphenotypes. Nature Communications. DOI: 10.1038/s41467-026-74190-x. https://www.nature.com/articles/s41467-026-74190-x
