ILD covers a wide range of pathological conditions that lead to progressive lung destruction and scarring.

Interstitial lung disease (ILD) has long presented a vexing (and often baffling) picture to patients and their clinicians. In the strictest sense, ILD may be a misnomer, since this condition affects not only the interstitium, but also the alveolar space and, at times, the airways. The pulmonary interstitium is, in effect, the space between the air-space epithelium and the endothelial cells lining the vasculature.¹ Consequently, diffuse parenchymal lung disease (DPLD) may be a more appropriate term.² ILD continues to be the commonly recognized name, however, and it is a convenient blanket term for a wide range of pathological conditions leading to progressive lung destruction and scarring.

The umbrella term ILD covers more than 200 discrete conditions associated with the cause of the disease. The specific causal agents create an immune reaction, generating the formation of fibrous nodules. As the disease progresses, fibrous tissue increasingly replaces elastic lung tissue. Loss of lung function is signaled by dyspnea, wheezing, coughing, and difficulty in expectorating.

The disease can be the result of almost any kind of lung insult. Its causes include inhaling organic or inorganic dusts such as asbestos, silica, heavy metals, and hay; inhaling toxic gases such as ammonia, chlorine, sulfuric acid, and hydrochloric acid; reacting to drugs such as amiodarone, narcotics, salicylates, terbutaline, oxygen, and paraquat; and metabolic disorders such as cystic fibrosis and lipoidoses. Causative respiratory infections can be bacterial (Legionella species); viral (cytomegalovirus, influenza, respiratory syncytial virus, and HIV); or fungal (Pneumocystis carinii). Interstitial lung diseases can be the result of a wide array of additional causes, including rheumatoid arthritis, sarcoidosis, renal failure, hepatitis, congestive heart failure, and recurrent aspiration. Many ILDs have been given descriptive names associated with the occupation or activity responsible for the patient’s exposure to a causative agent and the resulting pneumoconiosis. These names include black lung, farmer’s lung, hot-tub lung, bird-fancier’s disease, and many others.

The blanket term provides an expedient means of describing conditions that present similar clinical pictures. The causative agent is identified in fewer than 20% to 30% of patients with ILD.³ The cases of unknown cause have sometimes been classified as idiopathic pulmonary fibrosis (IPF), which is one of several idiopathic interstitial pneumonias, and is now recognized as a distinct clinical disorder.⁴ Adding to the potential confusion is a history of inconsistency in naming the conditions (and, in some cases, diametrically opposed opinions on how to manage them best). The terms DPLD, ILD, pulmonary fibrosis, and IPF continue to be used to describe the same condition.

ATS/ERS International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. Am J Respir Crit Care Med. 2002;165(2):277-304.
Copyright American Thoracic Society. Reprinted with permission.

It may be useful to think of IPF as a distinct type of idiopathic interstitial pneumonia, which is, in turn, a subset of ILD. In 2001, a joint commission⁵ of the American Thoracic Society and the European Respiratory Society approved a multidisciplinary consensus for the classification of the idiopathic interstitial pneumonias in an effort to bring order to a potentially chaotic set of conditions (see figure). Conditions categorized as falling under the umbrella of idiopathic interstitial pneumonia are IPF, nonspecific interstitial pneumonia, acute interstitial pneumonia, cryptogenic organizing pneumonia, respiratory bronchiolitis, desquamative interstitial pneumonia, and lymphoid interstitial pneumonia.

Various conditions have long been categorized in conflicting ways, but the international consensus statement⁵ offers a guideline for organizing current understanding of these diseases in a consistent way. It clarifies the terminology, definitions, and descriptions used in clinical practice. Most important for optimal respiratory care of these patients is an understanding of the elements that the conditions within ILD/DPLD have in common.

Clinical Presentation
By the time ILD patients seek medical attention, they can present with a wide range of symptoms, from mild dyspnea to severe incapacitation. Dyspnea, especially with exercise, is often the first clue. Fevers, chills, and night sweats may also manifest themselves. A careful, detailed patient history focusing on work, home life, environmental exposures, hobbies, medications, and family history is often a critical element in identifying the cause of ILD. Success or failure here can be a matter of life or death for the patient. Identifying and eliminating the causative agent (when possible) is central to successful treatment. Once the cause has been identified, treatment plans and outcomes still vary significantly, but where there is no identifiable causative agent (as in idiopathic pulmonary fibrosis), the prognosis may be very poor.

Chest radiographs will typically reveal diffuse interstitial infiltrates; this hazy increase in lung density is often referred to as a ground-glass appearance. Lung-function studies reveal decreased diffusing capacity of the lung for carbon monoxide resulting from the fibrosis associated with lung scarring. Likewise, a reduced forced vital capacity is expected, indicating a restrictive defect.^3,5

The use of high-resolution CT is an important advance in the diagnosis and staging of ILD. Sections of 1 mm to 2 mm are imaged to detect two distinct patterns of disease: a ground-glass increase in attenuation and a reticular pattern. The ground-glass appearance is associated with a histologic cellular appearance of that area of the lung; the reticular pattern is found in patients whose subsequent lung biopsies confirm fibrosis. High-resolution CT is significantly more sensitive and specific than chest radiography for the diagnosis of ILD and for the assessment of both the extent and the severity of the disease.^3,6

Further investigation often includes bronchoscopy. A bronchoalveolar lavage (BAL) test floods a segment of the lung with approximately 60 mL to 100 mL of saline, which is then pulled, via suction, into a sterile specimen trap for diagnostic cytology and histology. These studies may identify the antagonist causing the inflammatory process, in addition to excluding other possible diagnoses (such as lung cancer). BAL testing’s sensitivity may be more than 90%, with nearly 100% specificity for P. carinii infections, in particular.^7,8 A transbronchial biopsy using forceps is the accepted standard for differentiating between other possible causes of ILD. If questions remain following a transbronchial biopsy, the gold standard for diagnosis is a surgical (open) lung biopsy, although the associated risks make it a less attractive first choice. For IPF, transbronchial biopsy is not usually diagnostic, and surgical lung biopsy is ultimately required.³

Diagnosis is often a dynamic process that is amended as additional pieces of the puzzle become available. The final diagnosis should be rendered only after the pulmonologist, radiologist, and pathologist have reviewed all the data obtained from the patient.⁵

Treatment
Once healthy lung tissue has been destroyed by scarring, it cannot be repaired. Left untreated, many ILDs will continue to progress, with lung function deteriorating rapidly. Oxygen therapy may be required as the condition progresses and respiratory insufficiency increases. In these cases, frank discussions with the patient and family about the initiation of ventilator support should be undertaken. Lung transplantation may offer hope for select individuals with advanced disease who meet transplantation criteria.

The most important element in the successful treatment of ILD is eliminating the causative agent after it has been identified; this drives the often exhaustive search for a cause of the disease. If no agent is found, therapy can be directed toward suppression of inflammatory and cellular immune responses.³ Because an ongoing inflammatory process is a central element in some ILDs, corticosteroids may be of benefit.

There is considerable debate about the value of corticosteroids in treating IPF, which is, arguably, one of the most troublesome members of the ILD family. Its mortality rate is approximately 50% at 5 years.³ Treatment options are extremely limited (and recommendations are conflicting). One author,⁹ for example, claims that inflammatory mechanisms are a minor component of the pathogenesis of IPF, so anti-inflammatory drugs have little or no effect. Meanwhile, another author¹⁰ defends the practice, arguing that inflammatory mechanisms are not a minor component.

Immunosuppressive or cytotoxic agents may be considered for patients for whom corticosteroids appear to have failed. Supportive care, including influenza immunization, bronchodilators, supplemental oxygen, and pulmonary rehabilitation programs, can help the patient live with lungs that have been permanently damaged by ILD. Unfortunately, clinicians often face patients’ therapy using drugs and treatment plans that may have serious side effects, or may withhold treatment until the condition has progressed to a point at which there is little choice remaining. Improvements in lung function are uncommon, and prevention of further deterioration is often the most optimistic outcome that can be offered.

ILD represents a large family of lung disorders. That family continues to grow as clinicians and researchers learn more about the diverse causes of ILD. Some members of the family are much more sinister than others, and outcomes are closely related to the clinician’s ability to identify and eliminate the antagonist that instigated the condition.

John A. Wolfe, RRT, CPFT, is a contributing writer for RT and a member of RT’s editorial advisory board.

References
1. Schlenker EH. Cardiopulmonary anatomy and physiology. In: Hess DR, MacIntyre NR, Mishoe SC, Galvin WF, Adams A, Saposnick AB, eds. Respiratory Care: Principles and Practices. Philadelphia: WB Saunders; 2002:277-298.
2. Huaringa AJ, Leyva FJ. Diffuse parenchymal lung disease: a practical approach. The Internet Journal of Pulmonary Medicine.TM Available at: http://www.ispub.com/. Accessed January 6, 2005.
3. Ghio AJ. Interstitial lung disease. In: Hess DR, MacIntyre NR, Mishoe SC, Galvin WF, Adams A, Saposnick AB, eds. Respiratory Care: Principles and Practices. Philadelphia: WB Saunders; 2002:955-967.
4. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS) and the European Respiratory Society. Am J Respir Crit Care Med. 2000;161(2 Pt 2):646-664.
5. American Thoracic Society/European Respiratory Society. International multidisciplinary consensus: classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2002; 165(2):277-304.
6. Muller NL. Clinical value of high resolution CT in chronic diffuse lung disease. Am J Roentgenol. 1991;157(6):1163-1170.
7. Carter C, Stone MK. Respiratory microbiology, infection, and infection control. In: Hess DR, MacIntyre NR, Mishoe SC, Galvin WF, Adams A, Saposnick AB, eds. Respiratory Care: Principles and Practices. Philadelphia: WB Saunders; 2002:255-276.
8. Paradis IL, Grgurich WF, Dummer JS, Dekker A, Dauber JH. Rapid detection of cytomegalovirus pneumonia from lung lavage cells. Am Rev Respir Dis. 1988;138(3):697-702.
9. Gauldie J. Pro: Inflammatory mechanisms are a minor component of the pathogenesis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2002;165(9):1206-1207.
10. Strieter RM. Con: Inflammatory mechanisms are not a minor component of the pathogenesis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2002; 165:1206-1207.