Introduction drug induced pneumonitis.
Drug induced pneumonitis is a type of non-infectious lung tissue inflammatory disease
categorized by infiltration of interstitial and alveolar (Cui et al., 2017). Interstitial
pneumonitis involves the pleura, multiple structures of the respiratory system, airways, lung
parenchyma, mediastinum, pulmonary vasculature and the neuromuscular system (Yonemori
et al., 2016). This often exhibits as a dyspnea, dry cough, chest tightness, low grade fever,
pain, tachypnea, tachycardia, cyanosis, and fatigue. The most common form of drug induced
lung injury is drug-induced interstitial pneumonitis. Pneumonitis can cause permanent
respiratory failure which requires chronic oxygen therapy (Yonemori et al., 2016).
Pneumonitis is a side effect associated with several cancer treatments, including radiation
therapy and chemotherapy as well as newer targeted drugs and immunotherapies (Yonemori
et al., 2016).
Pembrolizumab is a monoclonal antibody that binds to the programmed cell death protein 1
(PD-1) receptor and targets programmed death-ligands 1 (PD-L1) found on T-cells and 2
(PD-L2), releasing PD-1 pathway-mediated inhibition of anti-tumor proliferation.(Pai?Scherf
et al., 2017). A severe adverse effect of Pembrolizumab is pneumonitis, which may cause
significant morbidity and mortality (Kwok, Yau, Chiu, Tse & Kwong., 2016). The median
time from the initiation of therapy to pneumonitis was 2 to 6 months, even though it could
occur after one to two doses of a PD-1/PD-L1 inhibitor (Li et al., 2017).
Mdm. Ken is currently admitted for shortness of breath for few weeks and she was noted to
be long standing dyspnea for few weeks after she was started on Pembrolizumab, Low
percutaneous arterial oxygen saturation, cough, fatigue, loss of appetite, loss of weight and
increasing requirement of oxygen therapy. The issue identified in this admission includes,
lower back pain. The purpose of this essay the author has no previous experience of
managing drug induced pneumonitis. Therefore the author will focus and discuss on
pneumonitis and diagnosis and management. Ken was also noted to need minimal assistance
in her ADL.
Pneumonitis diagnosis and management
Pembrolizumab demonstrates significant improvement in progression free survival and
overall survival for patients to compare with chemotherapy (Pai?Scherf et al., 2017).
However due to the Pembrolizumab, patients are often exposed to higher risk of pneumonitis
compared with routine chemotherapy (Wu, Hong, Zhang, Lu & Miao., 2017).
To rule out pneumonitis, it is important to evaluate promptly for any worsening respiratory
symptoms and treat if symptoms present (Lewis., 2016). Pneumonitis usually graded based
on the severity of the clinical symptoms and radiographic changes. Grade one pneumonitis is
characterized by radiographic changes and clinically asymptomatic. Grade two characterized
by mild to moderate respiratory symptoms, whereas grade three and four pneumonitis will
cause severe respiratory symptoms and limit patient’s self-care activities of daily living.
Examples: hypoxia, cough dyspnea, fever, chest tightness (Cui et al., 2017). The diagnosis of
pneumonitis should include a physical examination, chest X-ray, High-resolution computed
tomography (CT) scan, Arterial blood gas (ABG) analyses and full blood count, blood
aerobic and anaerobic cultures, echocardiogram(ECG), sputum Gram stain and culture
Physical examination and history taking is very important which includes details of all recent
drugs taken by the patient any reaction or side effects to drugs, Type of reaction such as
itching, urticaria, skin rash, respiratory difficulty, cigarette smoking and alcohol drinking,
monitoring vital signs and measuring percutaneous arterial oxygen saturation, palpate for
superficial lymph nodes for enlarged lymph nodes, auscultate the chest to examine for the
breathing differences between left and right side of lung for the presence of crepitate rales
and for airway lesions (Kubo et al., 2013).
Chest X ray is the first radiological investigation in pneumonitis patients, which will help in
establishing disease progression and chronicity (Mikolasch, Garthwaite & Porter., 2017).
Mdm. Ken’s chest X-ray shows, patchy consolidation in the right lower zone, venous
congestion and diffuse septal lines are present and ECG showed sinus tachycardia and
troponins were negative.
CT scans may show diffuse areas of ground-glass opacity with intra lobular interstitial
thickening as the major findings in anti-neoplastic agent induced pneumonitis (Matsuno.,
2012).CT scan helps to evaluate the extent to upper middle and lower lung (Nishino et al.,
2016). Mdm. Ken’s CT scan shows, Left supra clavicular lymph nodes are palpated which
corresponds to the findings of the computed tomography (CT) scan of the thorax, abdomen
and pelvis, And also showed innumerable nodules and ground glass opacities in bilateral
lungs, The smooth septal thickening in the left lung, patchy opacity is seen in the right lower
lobe and bilateral pleural effusion. Which are indicative pattern of pneumonitis Apart from
the pneumonitis, there were no other significant abnormal findings.
Arterial blood gas (ABG) analysis may be useful in individual patients before initiating
therapy with a drug known to cause pulmonary toxicity, especially in cancer patients. ABG
used to asses gas exchange and lung function (Mohammed & Abdelatief., 2016). A blood gas
obtained from the patient on 4 L/minute of nasal O2 demonstrated a pH of 7.46, pCO2 42.2
mm Hg, and pO2 106.6 mm Hg. Blood culture test used to identify infection and type of
micro-organism causing infection. Prophylactic Broad-spectrum antibiotics were started for
Mdm. Ken while waiting for blood culture, sputum gram stain and culture results. All
cultures and gram stain for infections were negative.
Pneumonitis treatment includes discontinuing immunotherapy treatment especially in grade
three and four pneumonitis, corticosteroid therapy, oxygen therapy, pulmonary rehabilitation
(Eigentler et al., 2016). Mdm. Ken’s treatment was discontinued. The initial treatment is
administering high doses of intra venous corticosteroids one to two milligram per kg per day
and required to taper the dose over few weeks if symptoms improved (Lewis., 2016).
Corticosteroids are Immunosuppressive anti-inflammatory agents and it helps to reduce
inflammation of the lung by suppressing the immune system (Meyer., 2014). However,
suppressed immune system increase the risk of developing infections, frail bones, insomnia
therefore corticosteroids can be dangerous (Meyer., 2014). Hyperglycemia is the most
common side effect of corticosteroids which will increases the glucose levels up to 68%
compared to baseline. Therefore it is essential to monitor blood glucose level from the start of
corticosteroids (Tamez-Pérez., 2015). Mdm Ken was started on IV dexamethasone 8 Mg
TDS for four days and tapered to 8Mg BD and blood glucose was monitored twice a day.
The aim of pulmonary rehabilitation is to decrease symptoms, optimize functional state,
increase participation there by improve quality of life. Pulmonary rehabilitation program
includes patient education on exercise to strengthen essential muscle groups, lower and upper
extremity exercise, breathing technique using incentive spirometry, diaphragmatic breathing,
and pursed lip breathing, respiratory therapy evaluation(Sharma & Singh., 2011). Progressive
weight loss occurs from inadequate dietary intake, increased resting energy expenditure.
Malnourishment will leads to imbalance in energy and weight loss. Therefore early screening
and proper management is important. Nutritional status should help to improve the state of
health, respiratory muscle function (Sharma & Singh., 2011). Mdm. Ken was referred to
physiotherapy and nutritional therapy.