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Drug-Induced Pulmonary Toxicity Clinical Presentation

  • Author: Ryland P Byrd, Jr, MD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
 
Updated: Dec 31, 2015
 

History

Drug-induced lung diseases have no pathognomonic clinical, laboratory, physical, radiographic, or histologic findings. Drug-induced lung disease is usually considered a diagnosis of exclusion (eg, after eliminating infectious and other causes). Discontinuance of the offending agent is often followed by spontaneous improvement, whereas failure to appreciate the causal relationship between the drug and the pulmonary disease can lead to irreversible lung injury.

Unfortunately, certain aspects of drug-induced disease can hinder the recognition of this cause-and-effect relationship. Although many drugs can cause diffuse infiltrative lung disease, very few of the patients who receive those drugs experience this disease. In the case of cytotoxic drug-induced disease, respiratory symptoms may not appear until many weeks after the last exposure to the drug. Finally, the drugs that cause diffuse infiltrative lung disease are often prescribed for conditions that are themselves associated with an increased risk for the disease.

Thus, clinicians evaluating patients with possible drug-induced pulmonary symptoms must obtain a thorough drug exposure history, maintain a high index of suspicion, and use a systematic diagnostic approach to make the correct and firm diagnosis. Irey[1] defined the following set of criteria for the diagnosis of drug reactions:

  • Correct identification of the drug, its dose, and its duration of administration
  • Exclusion of other primary or secondary lung diseases
  • Temporal eligibility - Appropriate latent period (exposure to toxicity)
  • Recurrence with rechallenge (a practice not commonly performed)
  • Singularity of drug (ie, other drugs the patient is taking)
  • Remission of symptoms with removal of the drug
  • Characteristic pattern of reaction to a specific drug (perhaps previous documentation)
  • Quantification of drug levels that confirm abnormal levels (especially for overdoses)
  • Degree of certainty of drug reaction (ie, causative, probable, or possible)
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Physical Examination

The physical findings of drug-induced lung disease are nonspecific. The patient may have crackles in the case of noncardiac pulmonary edema (NCPE), wheezes in the case of bronchospasm, and decreased breath sounds in pleural effusion. Furthermore, bibasilar “Velcro crackles” may be audible in cases of drug-mediated interstitial lung disease.

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Contributor Information and Disclosures
Author

Ryland P Byrd, Jr, MD Professor of Medicine, Division of Pulmonary Disease and Critical Care Medicine, James H Quillen College of Medicine, East Tennessee State University

Ryland P Byrd, Jr, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Coauthor(s)

Thomas M Roy, MD Chief, Division of Pulmonary Disease and Critical Care Medicine, Quillen Mountain Home Veterans Affairs Medical Center; Professor of Medicine, Division of Pulmonary Disease and Critical Care Medicine, Fellowship Program Director, James H Quillen College of Medicine, East Tennessee State University

Thomas M Roy, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Thoracic Society, Southern Medical Association, Wilderness Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Acknowledgements

Arshad Ali, MD Attending Physician, Department of Pulmonary and Critical Care Medicine, Mercy General Hospital of Sacramento

Arshad Ali, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society

Disclosure: Nothing to disclose. M Frances J Schmidt, MD Chief of Pulmonary Medicine, Pulmonary Fellowship Program, Teaching Attending Physician, Department of Medicine, Interfaith Medical Center

M Frances J Schmidt, MD is a member of the following medical societies: American College of Chest Physicians and American College of Physicians

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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Standard nonenhanced axial thoracic CT scan shows left lower lobe consolidation with some loss of volume and an air bronchogram. Transbronchial lung biopsy confirmed the diagnosis of cryptogenic organizing pneumonia.
CT scan of a patient with sarcoidosis illustrating multiple nodules. This pattern can manifest in patients taking medications that can cause granulomatous reactions.
Histologic section of the lung showing diffuse alveolar damage in a patient with adult respiratory distress syndrome.
In usual interstitial pneumonitis or idiopathic pulmonary fibrosis, subpleural and paraseptal inflammation is present, with an appearance of temporal heterogeneity. Patchy scarring of the lung parenchyma and normal, or nearly normal, alveoli interspersed between fibrotic areas are the hallmarks of this disease. In addition, the lung architecture is completely destroyed.
Cryptogenic organizing pneumonia (also called bronchiolitis obliterans-organizing pneumonia or BOOP) is often patchy and peribronchiolar. The proliferation of granulation tissue within small airways and alveolar ducts is excessive and is associated with chronic inflammation of surrounding alveoli.
Lung biopsy specimen from the patient with sarcoidosis (see CT scan illustrating multiple nodules). Multiple areas of noncaseating granulomas are present. Drugs such as methotrexate, nitrofurantoin, procarbazine, and pentazocine can cause granulomatous lung disease.
Close-up view of a noncaseating granuloma with a giant cell.
 
 
 
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