Tony Breu

Tony Breu

03-09-2022

18:15

1/14 🤔Why does it take weeks for the radiographic evidence of pneumonia to clear? Patients often feel better DAYS after starting treatment. And yet the chest x-ray takes WEEKS to return to normal. Why the delay?

2/ Early in pneumonia, neutrophils quickly attend to bacteria. The result is a chest X-ray (CXR) infiltrate containing: ➤edema ➤fibrin ➤neutrophils with engulfed bacteria ➤RBCs ➤desquamated epithelial cells This is seen in the first 4 days.

3/ In addition to our endogenous (neutrophilic) response, we also administer antibiotics to those diagnosed with pneumonia. But we stop them long before the infiltrate used to diagnose pneumonia resolves. Why?

4/ 🔑 Decades ago we learned that bacteria quickly disappear from sputum once antibiotics are administered. This is part of the basis for short-duration regimens in pneumonia: if the bacteria are quickly killed, long courses are not required.

5/ The swift bacterial killing leads to reduced production of exogenous pyrogens. This may explain the equally swift resolution of fever. 🔑 The average time to defervescence in pneumonia is just 2-3 days.

6/ So, around day 5 bacteria have been removed and neutrophils are no longer the main immune cell. And yet we still see an infiltrate on CXR. 🔑 In fact, early studies suggest that consolidations remain for up to 6-8 weeks.

7/ What is in this infiltrate if it isn't bacteria and neutrophils? Answer: MACROPHAGES And what are these macrophages doing? Answer: EFFEROCYTOSIS!

8/ Efferocytosis is the removal of apoptotic bodies (e.g., neutrophils with engulfed bacteria) by macrophages. How does this happen? 🔑 Apoptotic cells increase the exposure of phosphatidylserine. This is recognized as an “eat-me” signal by macrophages!

9/ Efferocytosis prevents secondary necrosis and the release of proinflammatory molecules from apoptotic bodies. 🔑 More effective efferocytosis has been linked to improved symptomatic recovery after pneumonia.

10/ Some bacteria are able to alter efferocytosis to their advantage. For example... 🦠 Klebsiella pneumoniae impedes efferocytosis by preventing phosphatidylserine expression on the surface of apoptotic neutrophils.

13/ Before closing, it's worth noting that impaired efferocytosis has been linked to other conditions characterized by chronic infiltrates. These include... ➤Idiopathic pulmonary fibrosis ➤Cystic fibrosis ...among others.

14/14 - SUMMARY ☞The initial infiltrate in pneumonia contains neutrophils and bacteria ☞The later infiltrate - seen up to weeks after clinical stability - is largely made up of macrophages engaging in efferocytosis, cleaning up apoptotic debris



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