Interstitial Lung Disease

The interstitial lung diseases (ILDs) are a collection of chronic lung conditions characterized by impaired gas exchange caused by abnormalities in the lung interstitium. ILDs may occur secondarily to connective tissue disease, medication, environmental or occupational exposures, infection, or cancer. A subset of these diseases occurs idiopathically, with idiopathic pulmonary fibrosis (IPF) being the most common. The approximate distribution of ILDs in the United States is depicted in the following figure:

(Source: Idiopathic Pulmonary Fibrosis. N Engl J Med 2018.)

Assessment

Etiology: In general, determining the underlying etiology of ILD is important to guide treatment and predict prognosis. The following common classification system is used to categorize the major subgroups of ILD and related causes:

(Source: Reproduced with permission from The Royal Australian College of General Practitioners from Troy L, Corte T. Interstitial Lung Disease in 2015: Where Are We Now?, Aust Fam Physician 2015;44(8):546-52.)

Pathophysiology: In pulmonary fibrosis, various triggers prompt exaggerated inflammatory cascades that lead to fibrotic tissue remodeling and extracellular-matrix deposition.

(Source: Spectrum of Fibrotic Lung Diseases. N Engl J Med 2020.)

Comprehensive history: When evaluating patients for suspicion of ILD, an important first step is to determine if the disease is secondary to a known cause. All patients should be asked about:

• onset of symptoms: The duration of symptoms may suggest a diagnosis (e.g., acute eosinophilic pneumonia and connective tissue-related ILD are associated with relatively acute onset of symptoms).

• history of autoimmune disease: including myositis, mixed connective tissue diseases, rheumatoid arthritis, scleroderma, Sjögren syndrome, and vasculitis

• medications and therapies: including amiodarone, nitrofurantoin, isoniazid, thiazides, sulfonamides, bleomycin, methotrexate, and radiation

• occupational or avocational exposure: including exposure to organic (e.g., spores or pigeon droppings causing hypersensitivity pneumonitis) and inorganic (e.g., coal, silicon dust, tobacco, or asbestos causing pneumoconiosis) substances

Quantitate pulmonary symptoms: In addition to asking about potential exposures, it is important to quantitate associated pulmonary symptoms, including dyspnea, cough, fatigue, and exercise tolerance. To quantitate symptoms, ask how far or long a person can walk or climb stairs without experiencing shortness of breath.

Physical exam: As with the history, the physical exam can help determine the potential etiology of ILD and the severity of the illness. Physical exam findings tend to reflect chronic hypoxemia. Therefore, it is important to examine for the following symptoms:

• cachexia

• resting tachypnea and accessory muscle use

• intercostal indrawing

• reduced chest wall expansion

• cyanosis

• digital clubbing

• Velcro-like crackles (can predate other clinical manifestations)

• pulmonary hypertension (in severe disease)

Dermatologic and musculoskeletal exams: Screen for possible rheumatologic conditions. Please refer to systemic sclerosis, inflammatory myopathies, rheumatoid arthritis, and undifferentiated inflammatory arthritis in the Rheumatology rotation guide.

Investigations

High-resolution computed tomography (CT) of the chest: In most cases, a high-resolution CT scan of the chest is mandatory for diagnosis. Other investigations (e.g., pulmonary function testing and 6-minute walk distance) can be used to monitor disease progression during follow-up.

The following investigations may be indicated depending on clinical context:

(Reproduced with permission from The Royal Australian College of General Practitioners from Troy L, Corte T. Interstitial Lung Disease in 2015: Where Are We Now? Aust Fam Physician 2015;44(8):546-52.)

Treatment

The treatment of ILD is dependent on the classification or the presence of an underlying cause. Once a diagnosis is made, first-line therapy is aimed at treating the underlying disease, usually with some form of immune modulating therapy. To date, most research on treatment has focused on idiopathic pulmonary fibrosis (IPF), the most common idiopathic interstitial pneumonia.

(Source: Spectrum of Fibrotic Lung Diseases N Engl J Med 2020.)

IPF treatment: No curative medical therapy at present exists for IPF. The following two antifibrotic agents have been approved for use in IPF. Studies suggest that these drugs slow the rate of decline in forced vital capacity but do not reverse established fibrosis, and a recent meta-analysis showed a mortality benefit associated with use of these agents.

• pirfenidone: an oral antifibrotic drug; adverse effects of pirfenidone include nausea, dyspepsia, fatigue, and photosensitivity

• nintedanib: an oral tyrosine kinase inhibitor; diarrhea is the primary adverse effect; also decreases the rate of decline in patients with systemic sclerosis and progressive fibrosing ILD

New targets of therapy currently being studied include phosphodiesterase-4 (PDE-4).

Read more about a general approach to diagnosis and management of ILD.