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: â€edema â€fibrin â€neutrophils with engulfed bacteria â€RBCs â€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 âeat-meâ 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.
11/ Other things affect efferocytosis. For example, smoking has been shown to inhibit efferocytosis and impair recovery after pneumonia.
12/ And what improves efferocytosis? There is some data that glucocorticoids and statins augment efferocytosis. The study in tweet 11 provides some of the evidence for the latter.
13/ Before closing, it's worth noting that impaired efferocytosis has been linked to other conditions characterized by chronic infiltrates. These include... â€Idiopathic pulmonary fibrosis â€Cystic fibrosis ...among others.
14/14 - SUMMARY âThe initial infiltrate in pneumonia contains neutrophils and bacteria âThe 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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