What Drugs Can Cause Lung Damage?: An Overview of Pulmonary Toxicity

With over 380 medications known to cause respiratory adverse effects, it is a critical topic for patients and healthcare providers. Understanding what drugs can cause lung damage is the first step toward prompt identification and management of potentially serious drug-induced lung injury (DILI).

Quick Summary

A diverse range of medications, from chemotherapy to antibiotics, can cause lung injury, leading to conditions like interstitial pneumonitis and fibrosis. Symptoms are often non-specific, requiring careful diagnosis by exclusion. Discontinuation of the causative drug is the cornerstone of treatment.

Key Points

• Diverse Drug Causes: A wide array of medications, including chemotherapy drugs (bleomycin), heart rhythm agents (amiodarone), and antibiotics (nitrofurantoin), can cause lung damage.

• Nonspecific Symptoms: Signs of drug-induced lung injury are often general and can be confused with other illnesses, making early diagnosis challenging.

• Varied Presentation: Lung damage can manifest as acute hypersensitivity reactions or chronic, insidious fibrosis, with different underlying mechanisms.

• Diagnosis of Exclusion: Establishing a diagnosis typically involves ruling out other potential causes, such as infection or underlying disease, through a detailed history and diagnostic tests.

• Drug Discontinuation is Key: The most critical step in managing drug-induced lung damage is promptly stopping the causative medication.

• Potential for Irreversible Damage: While many cases improve with drug cessation, especially with corticosteroid treatment, some chronic forms of damage can become irreversible.

Drug-induced lung injury (DILI) is a significant and often underrecognized side effect of many therapeutic agents, impacting the airways, lung parenchyma, pleura, and pulmonary vasculature. These adverse reactions can manifest acutely, subacutely, or chronically, with unpredictable onsets ranging from days to years after starting treatment. The challenge in diagnosing DILI lies in its nonspecific clinical and radiographic features, which often mimic other respiratory illnesses.

Mechanisms of Drug-Induced Lung Damage

Medications can harm the lungs through several pathways. Understanding these mechanisms helps explain the variety of pulmonary toxicities that can occur.

• Oxidative Injury: Some drugs produce reactive oxygen species (ROS) that overwhelm the lung's natural antioxidant defenses, leading to cellular damage. This process, known as oxidative stress, is a key mechanism for agents like bleomycin and nitrofurantoin, and it can eventually incite an inflammatory and fibrotic reaction.
• Immune-Mediated Injury: Drugs can act as antigens, triggering an immune cascade that damages lung tissue. This hypersensitivity reaction is believed to cause acute pneumonitis associated with drugs like methotrexate and nitrofurantoin. The reaction does not follow a simple dose-response relationship.
• Phospholipidosis: This mechanism involves the accumulation of phospholipids within alveolar macrophages and other lung cells. Amiodarone is a classic example of an amphiphilic drug that causes this cellular change, and while its presence confirms exposure, it does not always indicate active toxicity.
• Direct Cytotoxicity: Some chemotherapeutic agents, such as bleomycin, cause direct cellular injury by inducing DNA damage. This can lead to diffuse alveolar damage and ultimately pulmonary fibrosis.

Medications with Documented Pulmonary Toxicity

A wide array of drug classes have been implicated in causing lung damage. The severity and type of injury can vary greatly.

Chemotherapeutic and Immunosuppressive Agents

This class of drugs is a primary cause of drug-induced interstitial lung disease (DIILD), accounting for 23–51% of reported cases.

• Bleomycin: A well-known risk factor for pulmonary toxicity, bleomycin can cause a dose-dependent pneumonitis that may progress to irreversible fibrosis. Age, smoking, and prior radiation therapy increase the risk.
• Methotrexate (MTX): Used widely for cancer and rheumatic diseases, MTX can cause an acute hypersensitivity pneumonitis. Symptoms include fever, cough, and dyspnea, which typically resolve upon drug discontinuation.
• Immune Checkpoint Inhibitors (ICIs): A newer class of cancer drugs, ICIs like pembrolizumab and nivolumab can induce pneumonitis, often within the first few months of treatment.
• Busulfan, Carmustine, and Cyclophosphamide: These alkylating agents are known to cause pulmonary fibrosis, particularly with long-term use.

Cardiovascular Agents

• Amiodarone: Used to treat arrhythmias, amiodarone is one of the most common heart medications associated with pulmonary toxicity. The risk is linked to cumulative dose and duration of therapy. Toxicity can present as interstitial pneumonitis, organizing pneumonia, or acute respiratory distress syndrome (ARDS).
• Beta-Blockers: Certain beta-blockers can induce bronchospasm, especially in patients with asthma.

Antibiotics

• Nitrofurantoin: This antibiotic, used for urinary tract infections, can cause both acute hypersensitivity reactions and chronic lung injury leading to fibrosis after months or years of use.
• Sulfa Drugs: Sulfonamide antibiotics have also been associated with drug-induced lung disease.

Anti-Inflammatory Drugs

• Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Some NSAIDs, including aspirin, can cause hypersensitivity reactions resulting in bronchospasm in susceptible individuals.
• Gold Salts and Penicillamine: These older antirheumatic drugs have been linked to DIILD.

Illicit Drugs

• Cocaine and Heroin: Inhaled or injected illicit drugs can cause direct lung injury, including non-cardiac pulmonary edema, diffuse alveolar hemorrhage, and granulomatous pneumonitis, often related to injected fillers like talc.

Comparison of Acute vs. Chronic Drug-Induced Lung Injury

Drug-induced lung injury can present in various clinical patterns, with distinct characteristics depending on the timing of onset and underlying mechanism.

Feature	Acute Presentation	Chronic Presentation
Onset	Hours to weeks after drug exposure.	Months to years after initiation of therapy.
Symptoms	Fever, chills, cough, shortness of breath. Symptoms may be severe.	Insidious onset of dyspnea, nonproductive cough, and fatigue.
Mechanism	Often hypersensitivity reaction involving immune cells (e.g., eosinophils).	Often due to direct toxicity or cell-mediated response, leading to fibrosis.
Radiology	Bilateral interstitial or alveolar infiltrates, often with ground-glass opacities.	May show bilateral interstitial infiltrates, irregular linear opacities, and evidence of fibrosis or 'honeycombing'.
Prognosis	Usually rapid improvement after drug discontinuation, often with corticosteroids.	Slower improvement or potentially irreversible damage, especially with significant fibrosis.

Diagnosis and Management

Diagnosing DILI is a multi-step process that relies heavily on excluding other causes of pulmonary disease, such as infection, heart failure, or underlying systemic conditions. A thorough patient history, including all medications, supplements, and illicit drug use, is crucial.

Diagnostic tools include:

• Imaging: Chest X-rays can reveal nonspecific infiltrates, while high-resolution computed tomography (HRCT) provides detailed images showing ground-glass opacities, consolidation, or signs of fibrosis.
• Pulmonary Function Tests (PFTs): PFTs can show a restrictive pattern (decreased total lung capacity) and a reduced diffusing capacity of the lungs for carbon monoxide (DLCO).
• Bronchoalveolar Lavage (BAL): Analysis of fluid from BAL can show increased lymphocytes, neutrophils, or eosinophils, depending on the type of reaction.
• Biopsy: In complex cases, a lung biopsy may be required to confirm the diagnosis.

The primary step in management is the immediate and permanent discontinuation of the suspected causative drug. In severe cases, especially those with significant inflammation, a course of systemic corticosteroids may be initiated to hasten recovery. Supportive care, including supplemental oxygen, is also a critical component of treatment.

Conclusion

Drug-induced lung damage is a potential adverse effect of many different medications and substances, presenting a complex diagnostic and therapeutic challenge. Early recognition, based on heightened awareness of a patient's medication history and symptoms, is crucial for preventing irreversible lung damage. While diagnosis can be difficult and often relies on a process of exclusion, discontinuing the offending agent remains the most important step in management. In many cases, timely intervention can lead to a full or significant recovery, though chronic fibrosis can have long-lasting effects. For more information on pulmonary fibrosis, visit the Pulmonary Fibrosis Foundation.

Frequently Asked Questions

Can common antibiotics cause lung damage?

Yes, some antibiotics can cause lung damage. A prime example is nitrofurantoin, which is used for urinary tract infections and can lead to both acute allergic reactions and chronic interstitial lung disease with long-term use.

Which chemotherapy drugs are most likely to damage the lungs?

Chemotherapy drugs with a high risk of pulmonary toxicity include bleomycin, methotrexate, busulfan, and cyclophosphamide. Newer immunotherapy agents also carry this risk.

What is the risk of amiodarone-induced pulmonary toxicity?

The incidence of amiodarone-induced pulmonary toxicity is estimated to be between 1% and 5%, increasing with higher doses and cumulative exposure. It can manifest as acute or chronic interstitial pneumonitis.

How is drug-induced lung disease diagnosed?

Diagnosis of drug-induced lung disease is made by excluding other possible causes based on a patient's history, symptoms, imaging results (like chest CT scans), and pulmonary function tests. There is no single definitive test.

Are older adults at higher risk for drug-induced lung damage?

Yes, older age is a risk factor for drug-induced lung injury, particularly with chronic conditions and long-term drug use. For example, chronic nitrofurantoin-induced lung disease is seen predominantly in older women.

Can lung damage from a medication be reversed?

The reversibility of drug-induced lung damage depends on its type and severity. Acute reactions often resolve quickly after stopping the drug. However, chronic conditions like pulmonary fibrosis may result in irreversible scarring.

What are the common symptoms of drug-induced lung damage?

Common symptoms include nonproductive cough, shortness of breath (dyspnea), fever, and fatigue. The presentation can be acute with rapid onset or chronic with more insidious development.