Drug-Induced Lung Disease Imaging: An Overview.

Introduction:

With the advances in the therapeutic field, the list of adverse drug effects has also been increasing. The drugs undergo certain metabolic reactions within the body, targeting several vital organs. The primary site of action may also be targeted if administered in uncertain doses. Therefore, the toxic effects and sites may vary depending on the drug used. Skin, kidney, heart, liver, and lungs are the most plausible sites for adverse drug effects. However, the lungs are considered the target site for most drug toxic effects due to their larger contact surface and are also the primary site for most drug metabolic reactions.

What Is Drug-Induced Lung Disease?

Drug-induced lung disease is the possible adverse effect on the lungs caused by certain medications. The reaction may be specific or generalized. Studies have reported more than 380 known drugs responsible for drug-induced pulmonary diseases, which is bound to increase with therapeutic advancements. It may present with symptoms ranging from cough to severe respiratory distress syndrome. The drug response may vary between individuals as other factors such as environment, genetics, and certain intrinsic factors may also play a vital role in drug reactions. Drug-induced lung disease may affect the airways, pleura, mediastinum, muscles, neurovascular bundles, or even the lymph nodes.

Drug-induced interstitial lung disease is the most common form of drug-induced lung disease. It may be caused by oral, parenteral (intravenous), or intranasal forms of drugs. Adverse drug reactions may be severe and fatal; hence recognizing and treating them promptly is mandatory. Diagnosing drug-induced lung disease is complicated due to overlapping clinical and radiological findings. Therefore, advanced diagnostic tools such as computed tomography and a drug history form a base for diagnosing drug-induced lung diseases.

What Are the Causes of Drug-Induced Lung Disease?

Many medicines are known to cause lung diseases. Hence medical practitioners should be familiar with the possible adverse effects of the medications prescribed. A few of them are listed below:

• Antibiotics.

• Cardiac medicines.

• Chemotherapy drugs.

• Recreational drugs.

• Anti-inflammatory drugs.

• Immunosuppressive drugs.

What Are the Risk Factors Associated With Drug-Induced Lung Disease?

• Age: Children and elderly patients are more prone to developing adverse drug reactions.

• Sex: Females are more commonly affected, with studies reporting chronic pulmonary reactions.

• Dose: Drug dose is a significant risk factor for any drug reactions.

• Oxygen: Disruption of the oxidant and antioxidant balance may result in oxidative stress and severe respiratory distress syndrome.

• Drug Interaction: Co-administration of drugs in the same therapeutic genre could induce similar pulmonary toxicity.

• Underlying Lung Disease: Patients with preexisting lung disease are more prone to drug-induced lung diseases.

What Are the Types of Lung Diseases Caused by Adverse Drug Reactions?

Many types of lung diseases can occur due to medicines. They are given below:

• Allergic reactions like asthma and hypersensitivity reactions.

• Bleeding from the lung tissues or air sacs.

• Inflammatory reactions.

• Interstitial fibrosis (damage and scarring of lung tissues).

• Autoimmune diseases like drug-induced lupus erythematosus.

• Pneumonitis (inflammation of the air sacs).

• Vasculitis (inflammation of blood vessels).

• Pulmonary edema (accumulation of fluid in the lungs).

• Pleural effusion (fluid buildup between the lungs and the outer protective covering of the pleura).

• Pulmonary hypertension (increased arterial pressure of the lungs).

What Are the Symptoms of Drug-Induced Lung Disease?

The symptoms may be as below:

• Persistent cough.

• Fever.

• Chest pain.

• Bloody sputum.

• Difficulty in breathing.

• Shortness of breath.

• Wheezing.

What Are the Grades of Drug-Induced Interstitial Lung Disease?

• Grade 1: Mild- Asymptomatic with only positive radiological findings.

• Grade 2: Moderate- Symptomatic but not interfering with daily activities.

• Grade 3: Severe- Symptomatic and hampering the daily activities and oxygen level.

• Grade 4: Life-threatening- Assisted breathing (ventilator support) required.

• Grade 5: Fatal.

What Are the Imaging Techniques Used to Diagnose Drug-Induced Lung Disease?

Diagnosing drug-induced lung disease is difficult, considering the non-specific clinical symptoms and imaging findings. However, early diagnosis can help reverse the condition, preventing fatalities. The diagnostic workup is mentioned below:

• Radiograph: Chest X-ray is the preferred and initial diagnostic tool to identify pulmonary diseases as it is non-invasive, quick, and simple. However, the non-specific appearance and similarities to other pathologies, such as bacterial or viral infection, necessitate using other imaging modalities for a more confirmatory diagnosis. The most characteristic radiographic change is linear, nodular, or lace-like opacities. In addition, chronic cases may show fibrosis (scarring) with multiple nodules and lymphadenopathy.

• Computed Tomography (CT): Ground glass opacity (GGO) is a characteristic feature in CT of drug-induced lung disease. GGO is a sign indicating an active and treatable condition. High-resolution CT (HRCT) is of more diagnostic value in detecting pulmonary diseases, particularly reversible ones.

• Ultrasound: Ultrasound can assess pleural effusion and the intervention required.

• Nuclear Imaging: Nuclear imaging is more specific and sensitive to diagnosing drug-induced lung disease. A radio nuclear tracer (gallium-67) is primarily used in nuclear imaging. Patients with the active pulmonary disease have revealed intense uptake of the tracer material in the lungs. Nuclear imaging is vital in diagnosing the condition and even in assessing the response to treatment and prognosis.

• Pulmonary Function Tests: Pulmonary function tests are crucial to assess the functioning of the lungs. They are non-invasive and straightforward tests that can provide information on the extent of lung damage.

• Bronchoscopy: Bronchoscopy is a minimally invasive test that provides an accurate image of the lungs and the airways from the inside. It comprises a flexible tube that has a camera attached to its end. The scope would be inserted through the mouth or nose into the lungs and air sacs. A bronchoscopy-guided biopsy will help retrieve the tissue sample for further pathological investigations.

Conclusion:

Various drugs are known to cause pulmonary disease, and with novel therapeutic advances, the list of drugs causing adverse effects may increase. Drug-induced lung disease is reversible if diagnosed and treated promptly. However, a delay may cause potential pulmonary toxicity and may prove fatal. Considering the clinical and radiological features are non-pathognomonic, the need to rely on advanced imaging techniques such as HRCT and nuclear imaging becomes necessary. Hence, healthcare practitioners should be wary of the drugs that may cause adverse lung effects and consider the risk factors while prescribing.