Severe pneumonia may comprise three distinct “pneumotypes” with biological differences that could explain why some patients respond better to treatment and recover faster than others, new study findings suggest.
The research by Cambridge University Hospitals in the UK involved patients with severe pneumonia treated in intensive care units. Investigators studied immune cells, inflammatory signals and gene activity from fluid collected from patients’ lungs.
“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,” said Dr Mark Jeffrey, the study’s first author and a clinical researcher at the Department of Medicine at the University of Cambridge.
Looking at patterns of inflammation helped to highlight the differences, he added.
“Severe pneumonia is not a single disease, but several biologically distinct conditions that happen to look alike,” he added. “This helps explain why ‘one-size-fits-all’ treatments – including some immune-modulating drugs – have often failed in clinical trials.”
The researchers noted that treatments that work well for some subtypes may not work for others and may even worsen outcomes.
All three pneumotypes involved a similarly severe level of respiratory failure, a consistent proportion of which (58%) manifested with acute respiratory distress syndrome (ARDS).
They found that roughly half of patients (49%) had Pn1, which was characterised by a suppressed immune system and damage to the lining of the lungs. They had relatively low levels of inflammation, which may explain why inflammation-targeted treatments fail some patients.
Just under a quarter of patients (23%) were defined as having Pn2, which involved balanced immune activity and signs that their lungs were healing. They often recovered more rapidly, despite initially being as severely ill as other patients.
Finally, the third group (Pn3) required the most intensive mechanical ventilation and had the longest recovery periods. They also had high levels of inflammation in their lungs, making them most likely to benefit from treatments targeted at this condition.
The full study is published in Nature Communications [link here].
The authors noted that all three pneumotypes have comparable clinical presentations and severe respiratory failure but lead to divergent outcomes, indicating the need for individualised treatment.
The findings suggested patients with Pn3 might benefit from targeted immunomodulation alongside pathogen control, including approaches such as selective IL-6 blockade, the authors said.
The existence of other pneumotypes is likely, they added, and might be identified in larger cohorts.
“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,” said Dr Vilas Navapurkar from the John Farman Intensive Care Unit at Addenbrooke’s Hospital in Cambridge and a co-author of the study.
Such a personalised approach could help reduce pneumonia deaths, shorten ICU stays and cut unnecessary antibiotic use, he added.