Download Pneumonitis

PNEUMONITIS
What is it? What causes it? How do
I identify and treat it?
Our Lungs
• The lungs take the oxygen we
inhale and helps it enter the red
blood cell via the alveoli.
• Red blood cells then carry
oxygen around the body and
deliver to all cells.
• When the blood returns to the
lung, the CO2 is then transferred
back to the alveoli and we exhale
it.
Alveoli are tiny air sacs located at
the end of the bronchioles. They
have a very thin layer of cells and
an excellent blood supply.
Pneumonitis-Pathophysiology
A. Inflammation of the lung- in particular the alveoli
B. The thin layers of cells in alveolus are 97% Type 1 pneumocytes and
3% type 2 pneumocytes. The beginning stages of the injury start
with the death of Type 1 pneumocytes which makes the alveolar
wall vulnerable. This allows protein-rich exudates to leak into the
alveolar space. Hyaline membranes (fibrous membrane) then form
and cover the empty and damaged alveolar wall. This temporarily
walls the alveolus off from the rest of the body and inhibits
oxygen and CO2 delivery. After approximately 7 days, a period of
organization occurs and fibroblastic tissue fills the alveolar space
and the intersitium. Alveoli eventually recover or progress to
permanent fibrosis. Drugs may contribute to this pattern of
toxicity by causing apoptosis of epithelial cells and/ or by
inhibiting recovery during the organizing phase.
Some drugs cause an affect in the immune pathway- the insult activates the
coagulation pathway leading to the conversion of fibrinogen into fibrin
plugs. Fibrin is then laid down in the alveoli and eventually becomes a mass
mixed consisting of fibrin and histocytes.
Causative Agents
Chemotherapy
Non-chemotherapy
• All chemotherapies have the
potential to cause pneumonitis,
although some have a higher
incidence.
1. Bleomycin
2. Busulfan
3. Carmustine
4. Cyclophosphamide
5. Taxanes – Paclitaxel, Docetaxel
6. Methotrexate
1.
Radiation- either in thoracic
guided treatments (e.g-lung,
breast) or whole body rads in
preparation for transplant.
• Anti-tumor necrosis factor
monoclonal antibodies
1. Cetuximab (Erbitux)
2. Bevacizumab (Avastin)
3. Trastuzumab (Herceptin)
• PD-1 and PDL-1
1. Nivolumab
2. Pembrolizumab
3. Ipilumumab
Symptoms
DYSPNEA
DRY COUGH
FATIGUE
MAY PRESENT WITH:
LOW GRADE FEVER
ANOREXIA
Identifying
Differential
Diagnostics
• Can be TRICKY!!!!!
• Awareness of treatment
modalities and drugs
• Overall is a diagnosis of exclusion
• Lab draws are overall not helpful
with drug induced pneumonitis
• X-Rays
• CT
• Bronchoscopy with lavage
• Lung Biopsy
Treatment
1.
REMOVE the offending agent
1. Corticosteroids- mostly prednisone
2. At times mycophenalate Mofetil (MMF) will be used together
with prednisone
REMEMBER – EARLIER TREATMENT = BETTER OUTCOMES
AND….
WHAT
HAPPENS
NEXT
• Depending on the severity of the reaction
- If patient was still on active treatment it
is not uncommon to re-challenge them
once symptoms have resolved and they
have been weaned off steroids. Many
patients with a minor reaction (grade 1-2)
will go on to finish treatment without ever
having another episode.
• If they had a more severe reaction
(grade3/4) the drug is permanently
discontinued and should be placed on an
allergy list.
• Recurrence rates are not well
documented, known or understood.
Complications
• If not recognized and left untreated pneumonitis can lead to
pulmonary fibrosis- which can then lead to right heart failure,
respiratory failure and death.
• Pulmonary edema
• Pulmonary hypertension
• Hemorrhage and hemoptysis
Questions???