Discovery of 3 severe pneumonia subtypes could lead to tailored treatments

Cambridge researchers have shown that severe pneumonia has three different subtypes, helping explain why some patients in intensive care units (ICUs) recover from their illness faster than others, while for other patients the disease can be life-threatening.

Their findings could in future help inform tailored treatments, allowing individual patients to receive the most appropriate therapies.

Pneumonia is the most common infectious cause of death worldwide, responsible for an estimated 2.5 million deaths a 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.

Doctors have long struggled to understand why patients whose condition looks similar clinically can have very different recoveries. Some respond quickly to treatment, while others remain critically ill for weeks or even die.

Looking beyond clinical labels

Dr. Andrew Conway Morris from the Department of Medicine at the University of Cambridge and an ICU consultant at Addenbrooke’s Hospital, Cambridge, said, “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.

“The current approach of classifying patients by their clinical syndromes—sepsis, acute respiratory distress syndrome and so on—without looking at the underlying biology risks missing what’s key. Instead of asking ‘Does this patient have pneumonia?’ we should be asking ‘What’s the inflammatory pattern in this patient’s lungs?'”

In findings published in Nature Communications, Conway Morris and his team recruited patients admitted with suspected severe pneumonia to the ICU at Addenbrooke’s Hospital, part of Cambridge University Hospitals NHS Foundation Trust.

Severe pneumonia is usually diagnosed through a combination of symptoms, imaging and blood tests. Symptoms typically include fever or hypothermia, low oxygen levels, breathing difficulties and confusion.

Instead of relying only on blood tests or scans, however, the Cambridge team analyzed immune cells, inflammatory signals and gene activity in fluid taken from the lungs of the patients. They discovered that there are three distinct biological types—or “pneumotypes”—of severe pneumonia, none of which could be reliably detected using standard blood tests, even though they were strongly linked to how patients recovered.

Three patterns in the lungs

The most common pneumotype—accounting for almost half (49%) of cases—was characterized by immune suppression, significant damage to the lining of the lungs and bleeding in the alveoli (tiny air sacs within the lungs). There were fewer signs of inflammation, which may explain why treatments targeting inflammation can fail or even harm some patients.

The second pneumotype—accounting for just under a quarter (23%) of cases—was characterized by a balanced immune response and active repair of damage to the lungs. Patients were most likely to recover faster from this pneumotype and require the shortest time on the ventilator, even though they initially looked just as ill as the others.

Patients with the most dangerous pneumotype—the one that most resembles “classic” pneumonia—spent the longest on mechanical ventilation and had prolonged critical illness. They had severe and persistent inflammation, with a flood of immature immune cells in the lung. This group may be most likely to respond to anti-inflammatory therapies, the team said.

Dr. Mark Jeffrey from the Department of Medicine at the University of Cambridge, the study’s first author, said, “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.”

A route to tailored care

The tests used to determine the pneumotypes are too complex to enable rapid classification, but the researchers hope to develop a simplified tool that could help them stratify the patients and ultimately offer tailored treatments.

Dr. Vilas Navapurkar from the John Farman Intensive Care Unit at Addenbrooke’s Hospital said, “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.”

Who’s behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries.

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Robert Egan

Bachelor’s in mathematical biology, Master’s in creative writing. Well-traveled with unique perspectives on science and language.

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