Researchers identify three biological forms of severe pneumonia

Researchers at the University of Cambridge have identified three biological subtypes of severe pneumonia, a finding they say may help explain why ICU patients with similar clinical diagnoses can recover at very different speeds. The team said the work could eventually support more tailored treatment for critically ill patients, although the current tests are not yet suitable for rapid bedside use.

The findings, published in Nature Communications, come from a study of patients admitted with suspected severe pneumonia to the intensive care unit at Addenbrooke’s Hospital, part of Cambridge University Hospitals NHS Foundation Trust. According to the University of Cambridge, the researchers examined lung fluid for immune cells, inflammatory signals and gene activity rather than relying only on blood tests, imaging and symptoms.

Pneumonia is the leading infectious cause of death worldwide, causing an estimated 2.5 million deaths each year, according to the university. In severe cases, patients may require ICU care and mechanical ventilation, and the university said severe pneumonia accounts for six in 10 infections treated in intensive care.

Why similar cases can diverge

Cambridge said clinicians have struggled to explain why some patients who appear alike at admission improve quickly while others remain critically ill for weeks or die. Severe pneumonia is typically diagnosed using a mix of symptoms, scans and blood tests, with signs that can include abnormal body temperature, low oxygen, breathing difficulty and confusion.

Dr. Andrew Conway Morris, of Cambridge’s Department of Medicine and an ICU consultant at Addenbrooke’s, said the usual clinical labels, such as sepsis or acute respiratory distress syndrome, can miss the biology driving disease in the lungs. He said inflammation-targeting treatments have produced mixed trial results, with some studies suggesting benefit and others suggesting harm.

The Cambridge team said standard blood tests did not reliably reveal the subtypes it found in the lung samples. Those subtypes, which the researchers called pneumotypes, were strongly linked with how patients fared.

Three lung inflammation patterns

The most common subtype accounted for 49% of cases, according to the university. Cambridge said it showed immune suppression, major injury to the lung lining and bleeding in the alveoli, the small air sacs in the lungs, with fewer signs of inflammation than the other groups.

The researchers said that pattern may help explain why anti-inflammatory treatments do not help some patients and may harm them. In those patients, the problem may not be excessive inflammation, based on the lung biology described by the team.

A second subtype made up 23% of cases, according to Cambridge. The university said those patients had a balanced immune response and signs of active lung repair, and they tended to come off ventilators sooner despite initially appearing as sick as the other patients.

The third subtype was described by the team as the highest-risk pattern and the one most resembling classic pneumonia. Cambridge said those patients had severe, persistent inflammation and many immature immune cells in the lung, spent the longest time on mechanical ventilation and had prolonged critical illness.

Dr. Mark Jeffrey, the study’s first author, said patients who looked similar by illness severity, oxygen levels and clinical diagnosis had very different outcomes once lung inflammation patterns were analyzed. He said the results support the view that severe pneumonia includes several biologically distinct conditions that can look alike at the bedside.

Next step: simpler tests

The university said the analyses used in the study are too complex for fast classification in routine care. The researchers hope to develop a simpler tool that could group patients by subtype and guide treatment choices.

Dr. Vilas Navapurkar, from the John Farman Intensive Care Unit at Addenbrooke’s Hospital, said identifying a patient’s subtype could allow doctors to boost immune response in some cases and reduce harmful inflammation in others. Cambridge said such an approach could potentially help critically ill patients, reduce pneumonia deaths, shorten ICU stays and limit unnecessary antibiotic use.

The paper is titled “Pulmonary inflammation in severe pneumonia is characterised by compartmentalised and mechanistically distinct sub-phenotypes” and was published in Nature Communications. Cambridge listed the DOI as 10.1038/s41467-026-74190-x.

This story draws on original reporting from Medical Xpress.