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Drug-Induced Lung Disease - Causes, Risk Factors, Symptoms, and Management

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Drug-induced lung disease is caused due to a negative reaction to a medicine. Read this article to know more about this.

Written by

Dr. Vidyasri. N

Medically reviewed by

Dr. Kaushal Bhavsar

Published At September 20, 2022
Reviewed AtFebruary 28, 2024

Introduction:

Drug-induced pulmonary disease is not a single disorder but rather a common clinical problem. The affected patients present with various respiratory symptoms, deterioration of pulmonary function, histologic changes, or several of these findings associated with drug therapy. Depending on the drug, the syndromes can cause interstitial fibrosis, asthma, non-cardiogenic pulmonary edema, pulmonary eosinophilia, pleural effusions, or veno-occlusive disease.

What Are the Causes of Drug Induced Lung Disease?

Medicines cause many types of lung injury. It is usually impossible to predict who will develop lung disease from a medicine.

Types of lung problems that may be caused by medicines include:

  • Alveolar Hemorrhage- Bleeding into the lung air sacs or alveoli (alveolar hemorrhage).

  • Allergic Reactions - Asthma, hypersensitivity pneumonia, or eosinophilic pneumonia.

  • Bronchitis - Swelling and inflamed tissue in the main passage that carries air into the lungs.

  • Interstitial Fibrosis - Damage to the lung tissue.

  • Lung Vasculitis - Inflammation of lung blood vessels.

  • Lymph Node Swelling - Inflammation and swelling of the lymph nodes.

  • Pneumonitis- Inflammation of the lung air sacs (pneumonitis).

  • Granulomatous Lung Disease - A type of inflammation in the lungs.

  • Mediastinitis - Swelling and irritation of the chest area between the lungs.

  • Pulmonary Edema- An abnormal buildup of fluid in the lungs.

  • Pleural Effusion - A buildup of fluid between the layers of tissue that line the lungs and chest cavity.

  • Pulmonary Hypertension - Abnormal pressure of the arteries that bring blood to the lungs.

Many medicines and substances are known to cause lung disease in some people. These include:

  • Antibiotics, such as Sulfa drugs and Nitrofurantoin.

  • Chemotherapy drugs such as Methotrexate, Bleomycin, and Cyclophosphamide.

  • Heart medicines such as Amiodarone.

  1. Cancer Therapy Drugs- The most common cancer drugs causing lung disease are Bleomycin, Gemcitabine, Methotrexate, epidermal growth factor receptor (EGFR)- directed therapies, mechanistic target of rapamycin protein inhibitors (mTOR) inhibitors, and immune checkpoint inhibitors.

  2. Bleomycin: Bleomycin, used most commonly to treat Hodgkin’s lymphoma and germ cell tumors, causes lung injury through immune-mediated and direct toxic effects. The clinical presentation of Bleomycin lung injury is highly variable but can be asymptomatic. Pulmonary physiology changes are common and include an early reduction in diffusing capacity of the lung for carbon monoxide followed by changes in forced vital capacity (FVC), which correlates with symptomatic deterioration. Idiosyncratic reactions at low doses early in the treatment course are also less commonly observed.

  3. Gemcitabine: Gemcitabine is used to treat a wide range of cancers, including non-small cell lung cancer (NSCLC), breast cancer, and pancreatic cancer. Mortality rates are generally low except in severe cases requiring hospitalization. In contrast to Bleomycin, the timing of onset and dose relationship are less consistent. The risk of drug-induced interstitial lung disease is highest when combined with other drugs, especially Erlotinib, Taxanes, and Bleomycin.

  4. Epidermal Growth Factor Receptor (EGFR) - Targeted Agents: Epidermal growth factor receptor-targeted agents include small molecular receptor tyrosine kinase inhibitors (RTKIs) and monoclonal antibodies for the treatment of non-small cell lung cancer, colorectal cancer, and breast cancer. The drug-induced interstitial lung disease caused due to epidermal growth factor receptor-targeted agents and receptor tyrosine kinase inhibitors appears to be an early event. But studies of Gefitinib and Erlotinib report the highest incidence within four weeks of starting treatment.

  5. Mechanistic Target of Rapamycin Protein (mTOR) Inhibitors: Mechanistic targets of Rapamycin protein inhibitors are used predominantly in the treatment of renal cell cancers and neuroendocrine tumors and also as anti-rejection agents in solid organ transplantation. Sirolimus, Temsirolimus, and Everolimus are associated with pulmonary toxicity.

  6. Immune Checkpoint Inhibitors: Checkpoint inhibitors of programmed cell death 1 (PD-1) and its ligands (PD-L1 and PD-L2) and cytotoxic lymphocyte antigen protein 4 (CTLA-4) are involved in the treatment of metastatic melanoma, Hodgkin’s lymphoma, and non-small cell lung cancer. The incidence rate, mortality, and severity of drug-induced interstitial lung disease are all higher for PD-1 inhibitors compared with PD-L1 inhibitors.

  7. Methotrexate: Methotrexate is a mainstay agent in rheumatology and for the treatment of lymphomas and sarcomas. The chance of recurrence is approximately one-third of re-challenged cases and carries a high mortality.

  8. Antibiotics: Nitrofurantoin is most commonly used in the treatment and prophylaxis of urinary tract infections. Reports state that drug-induced interstitial lung disease accounts for 16 to 48 % of Nitrofurantoin-related adverse events. The hospitalization rate was 75%, and mortality rates were 0.5 % and eight percent, respectively, for patients with acute lung reactions and chronic interstitial pneumonia. An acute reaction occurs within days or hours if there has been previous Nitrofurantoin exposure. The most common underlying mechanism is a hypersensitivity reaction which resolves quickly in most cases. Chronic interstitial pneumonia rarely occurs, mimicking pulmonary fibrosis. It is more commonly seen in patients on long-term prophylaxis.

  9. Amiodarone: Amiodarone is the most common cause observed in drug-induced interstitial lung disease patients. Patients most commonly present with a subacute form of drug-induced interstitial lung disease, whereas acute and fatal forms can also occur. Symptomatic recovery in survivors occurred over a median of 36 months, with improvement in radiological features of alveolitis but a high rate of fibrosis. Cumulative dose is an important risk factor for Amiodarone-related drug-induced interstitial lung disease, and the combination of high doses over longer periods is more strongly associated with drug-induced interstitial lung disease than dose or duration alone.

What Are the Symptoms of Drug Induced Lung Disease?

  • Hemoptysis (coughing up blood or bloody mucus from the lungs and throat).

  • Chest pain.

  • Cough.

  • Shortness of breath.

  • Wheezing.

  • Fever.

What Is the Risk Factor for the Development of Drug Induced Interstitial Lung Disease?

Risk factors for the development of drug-induced interstitial lung disease vary according to the disease, drug, and population being treated. Certain risk factors have featured prominently across drugs.

  • Age: Increased age is identified as a significant risk factor for drug-induced interstitial lung disease for treatment with Bleomycin, Gemcitabine, Leflunomide, Methotrexate, Amiodarone, and Nitrofurantoin.

  • Smoking: Smokers are at increased risk when treated with Gemcitabine and Methotrexate.

  • Drug Dosage: A clear dose-dependent relationship is well recognized for Bleomycin, Amiodarone, and Nitrofurantoin.

  • Other Risk Factors:

  • Higher alcohol consumption.

  • Genetic susceptibility.

  • Renal dysfunction.

  • Diabetes.

What Is the Treatment Approach for Drug Induced Interstitial Lung Disease?

The first step is to stop the medicine that is involved in causing the disease. Other treatments are provided based on the underlying symptoms present. Oxygen therapy is maintained until the drug-induced lung disease improves. Anti-inflammatory medicines called Corticosteroids are most often used to quickly reverse lung inflammation.

Conclusion:

A proper diagnostic approach and timely management aid in the prevention of the progression of the disease. The prognosis for acute and chronic forms of the disease varies depending on the condition and provides positive outcomes after the medicine has been stopped. Certain drug-induced lung diseases, such as pulmonary fibrosis, may never clear away and can worsen even after the medicine is stopped and can result in death.

Frequently Asked Questions

1.

Which Medicines Cause the Most Common Respiratory Problems?

The two most common respiratory problems caused by medicines are:
 - Allergic reactions like asthma and eosinophilic pneumonia.
 - Alveolar hemorrhage is bleeding into the lungs' air sacs (alveoli).

2.

What Is Meant by Drug-Induced Lung Damage?

Drug-induced lung damage is a type of lung condition brought on by an adverse drug response in an individual. It can also be caused due to an allergic reaction to a particular drug.

3.

What Is the Treatment for Lung Injury Caused by Drugs?

As soon as medicines are established as the cause of lung injury, the drugs causing it should be stopped. Apart from that, the treatment is based on the symptoms being experienced by the patient. Oxygen therapy, along with corticosteroids, is required in most cases. Corticosteroids are anti-inflammatory drugs and thus help in reducing lung inflammation quickly.

4.

How Is Medication-Induced Pneumonitis Identified?

There are several methods to diagnose drug-induced pneumonitis: blood tests, lung function tests (spirometry and oximetry), bronchoscopy, CT (computed tomography) scan, X-rays of the chest, and lung biopsy.

5.

Which Drug Treats Lung Disease the Best?

The best medicine for the long-term management of lung disease currently available is inhaled steroids. They enhance lung function and reduce lung disease symptoms.

6.

What Medicines Cause Shortness of Breath?

NSAIDs (Non-steroidal anti-inflammatory drugs), beta-blockers, CCB (calcium channel blockers), ACE (angiotensin converting enzymes) inhibitors, antifungals, antibiotics, antimicrobials, medicines used for cancer treatment, anticonvulsants, cholinergic drugs, antihypertensives, Digoxin, interferon, and antiretrovirals are among the drugs that might cause shortness of breath.

7.

Which Two Drugs Are Responsible for Pulmonary Fibrosis?

The two medications that cause pulmonary fibrosis are Amiodarone (used in heart disease) and Bleomycin (used in cancer treatment).

8.

What Are the Warning Signs of Pneumonitis?

The early signs of pneumonitis are cough, breathlessness, tiredness, reduced appetite, and weight loss.

9.

How Much Time Does the Pneumonitis Treatment Take?

The pneumonitis treatment can take up to three months or longer, depending on the severity of the disease.

10.

Can Pneumonitis Disaapear by Itself?

Pneumonitis does not resolve independently, and it takes up to three months or more for the symptoms to resolve. Oxygen therapy and corticosteroids are recommended during the treatment course.

11.

Can Lungs Heal on Their Own?

When exposure to pollution is removed, the lungs will begin to restore themselves due to their self-cleansing nature. Avoiding hazardous chemicals like smoking and air pollution, exercising frequently, and eating healthily are the greatest ways to protect the lungs.

12.

Can Weak Lungs Heal themselves?

Weak lungs can be healed by doing normal breathing exercises and staying active. Posture correction and staying in a clean environment also contribute to the healing of weak lungs.

13.

Which Antibiotic Treats Pneumonia the Best?

Since pneumonia is a bacterial infection, it is best treated with antibiotics like Amoxycillin and Clavulanic acid, macrolides like Azithromycin, and Cephalosporins.

14.

Is There a Permanent Cure for Pneumonia?

While most people who get pneumonia will recover without any long-lasting complications, some may find it difficult to get well and never fully recover. Hence, preventive measures are very important for pneumonia treatment.

15.

How Do I Check Myself for Pneumonia?

For self-examination of the signs of pneumonia, an individual can look for signs like breathlessness, heaviness of the lungs, cough, tiredness, weight loss, changes in the breathing pattern and rate, and extreme tiredness.

16.

What Are Respiratory Danger Signs?

The signs of respiratory distress are wheezing, increased heart rate, persistent cough with phlegm, change in skin color or fingers, shortness of breath, chest retraction, and crackling breathing sounds.
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Dr. Kaushal Bhavsar
Dr. Kaushal Bhavsar

Pulmonology (Asthma Doctors)

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