US Pharm. 2013;38(7):37-39.
Gas exchange, necessary for life, is the essential
function of the lung. By virtue of this exchange, there are potential
insults arising from environmental agents—both infectious and
noninfectious—that jeopardize this function. Upon insult, if the normal
inflammatory and/or repair response is dysregulated, a chronic alveolar
or interstitial remodeling process ensues; inflammation and fibrosis
manifest in varying degrees.1 Ultimately, gas-exchange abnormalities and restrictive physiology constitute the characteristic pathology of diffuse interstitial lung disease. This term refers to a heterogeneous group of diseases sharing common clinical, radiographic, and physiological characteristics.1,2
Further, insults may arise via the
circulation; for example, from a systemic connective tissue disease such
as rheumatoid arthritis or systemic sclerosis, or from drugs and
treatments. Rheumatologists and other physicians often underestimate the
impact of the disorders associated with interstitial lung disease and
diagnose respiratory impairment when it has reached an irreversible
fibrotic stage.3 In conjunction with the rising median age of
the U.S. population, an increase in the use of pneumotoxic drugs to
treat malignancies and cardiovascular diseases in the elderly
contributes to an increased incidence of interstitial lung disease.1
It is difficult to assess the incidence of true drug-induced pulmonary
disease due to pulmonary nonspecificity and the interaction between the
current underlying disease and the drugs.4 Alternative names for diffuse interstitial lung disease that may appear in the medical record include diffuse parenchymal lung disease; alveolitis; and idiopathic pulmonary pneumonitis.
Etiology and Risk Factors
As noted above, the causes of diffuse interstitial lung
disease are many and include occupational and environmental factors,
medical conditions, drugs and treatments (TABLE 1, RESOURCE).
Lung damage may be caused by long-term exposure to various toxins and
pollutants, including asbestos fibers, silica dust, coal dust, grain
dust, and bird and animal droppings.2 Examples of medical
conditions that can result in damage to the lung include rheumatoid
arthritis, systemic lupus erythematosus, sarcoidosis, and systemic
sclerosis and scleroderma.2,5,6 Chemotherapeutic agents,
antibiotics, antiarrhythmic drugs, and immunosuppressive agents can
cause drug-induced interstitial lung disease; diagnosis is commonly made
when a patient with interstitial lung disease is exposed to a drug that
is known to induce lung disease and other causes have been excluded.7 When the cause of diffuse interstitial lung disease cannot
be determined, which happens to be the situation in most cases of this condition, it is termed idiopathic interstitial lung disease. Idiopathic pulmonary fibrosis
(IPF), a progressively worsening condition characterized by
inflammation and fibrosis, is the most prevalent and devastating of all
the diffuse interstitial lung diseases.1,5,8 TABLE 2 addresses the potential reasons why the elderly are particularly susceptible to IPF.
Symptoms and Complications
Irreversible lung damage often has already manifested by
the time symptoms appear; the primary signs and symptoms of diffuse
interstitial lung disease are shortness of breath aggravated by exertion
and a dry cough.2 As the disease progresses, patients may
develop clubbing (abnormal enlargement of the base of the fingernails)
and blue coloring of the lips, skin, or fingernails secondary to
cyanosis.5 Patients should not ignore breathing difficulties,
since early and accurate diagnosis is important for appropriate
treatment and management. TABLE 2 offers guidance for patients
regarding when to seek medical attention. Complications include
progressive pulmonary hypertension, right-sided heart failure (cor pulmonale), and respiratory failure.2
Diagnostic testing is imperative, since
differential diagnosis is challenging given the variety of disorders
that fall under the category of diffuse interstitial lung disease and
the spectrum of medical conditions that share their symptomatology.
Examples of testing procedures used to reach a definitive diagnosis include2
• Imaging tests: chest x-ray, CT scan, and echocardiogram
• Pulmonary function tests: spirometry, oximetry, exercise stress test
• Lung tissue analysis: bronchoscopy, bronchoalveolar lavage, surgical biopsy.
Medications and Treatment: Lung
scar tissue is irreversible and there are no current treatments that
prevent the ultimate disease progression that ensues. However, the goal
of medications and treatment is to improve symptoms temporarily and
potentially slow the current progress to some degree in an attempt to
improve quality of life.2 Primary treatment of interstitial
lung disease involves discontinuation of an offending agent and
avoidance of further exposure; suppression of active inflammation with
the use of systemic corticosteroids (e.g., prednisone) in patients with
symptoms or with progressive or disabling disease; and treatment of
complications and provision of supportive care.1,4,7
Sometimes the corticosteroid is coadministered with an immunosuppressant
(e.g., cyclosporine) as initial therapy; however, long-term
effectiveness has not been proven.2 Oxygen therapy is
palliative for breathing and exercise; it also prevents or reduces the
likelihood of complications secondary to hypoxia.2 In
addition to other benefits, the patient may report improvement in sleep
and sense of well-being; 24-hour oxygen may be required in some
individuals.2 Families should be guided regarding proper oxygen storage and safety.
Pulmonary Rehabilitation: In
order to improve and maximize daily functioning, pulmonary
rehabilitation focuses on improving endurance of physical exercise,
emotional support, and nutritional counseling to ensure adequate
calories and nutrients.2,5
Organ Transplantation: For
younger people with severe interstitial lung disease who have been
refractory to therapy, lung transplantation may be an option of last
health care by the patient is essential to living with diffuse
interstitial lung disease. Patients should be counseled regarding
options for quitting smoking, i
cessation therapies and programs; avoidance of harmful secondhand smoke
requires the patient to disallow others to smoke in their presence.2
A nutritionally rich diet containing adequate calories is imperative,
since patients with lung disease are prone to weight loss secondary to
burning extra calories just to breathe; nutritional counseling is
recommended. Immunizations offer protection against respiratory
infections that are capable of worsening the symptoms of interstitial
lung disease; the pneumonia vaccination and annual flu vaccination are
recommended. Of note, avoidance of illicit drug use may prevent a number
of drug-induced lung diseases.9
Patient and Caregiver Coping and Support
The physical and emotional challenges
associated with living with chronic lung disease often require
adjustments in the patient’s daily routines and activities to
accommodate progressive breathing problems and other health care needs.
Support groups or psychological counseling may provide comfort in coping
with the fear, anger, and sadness associated with the grieving process
that one experiences when transitioning from one’s previous active
lifestyle to one of a more debilitated state. Furthermore, assigning a
health care proxy, planning for and understanding hospice services,
including the provision of palliative and end-of-life care, are all
important issues to be discussed at appropriate times so that comfort
and care of the patient, and support and resources for the family, are
readily available at the time of need.
Genetics, age, and the environment
contribute to impaired regenerative capacity and fibrosis of lung
tissue. Occupational and environmental factors, medical conditions,
drugs, and treatments are all culprits. Diffuse interstitial lung
disease describes a large group of disorders, most of which cause
progressive, generally irreversible scarring of lung tissue; early
diagnosis is important. Discontinuation of the offending agent, use of
systemic corticosteroids, and supportive care is the primary treatment
and is best achieved through a multifaceted approach.
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2. Interstitial lung disease.
MayoClinic.com. Published July 9, 2011.
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3. Marigliano B, Soriano A, Margiotta D,
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it differ from IPF? How should the clinical approach differ? Chron Respir Dis. 2011;8:53-82.
9. Drug-induced pulmonary disease. MedlinePlus. U.S. National Library of Medicine. National Institutes of Health. Updated June 2, 2011.
www.nlm.nih.gov/medlineplus/ency/article/000104.htm. Accessed June 19, 2013.
10. Cooper JA, White DA, Matthay RA. State of the art: drug-induced pulmonary disease, Part I: Cytotoxic drugs. Am Rev Respir Dis. 1986;133:321-340.
11. Kehrer JP, Kacew S. Systematically applied chemicals that damage lung tissue. Toxicology. 1985;35:251-293.
12. Epocrates, Version 4.5. Epocrates, Inc. www.epocrates.com. Accessed June 19, 2013.
13. Harvey RA, Champe PC, eds. Pharmacology. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:205.
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