Idiopathic pulmonary fibrosis: What primary care physicians need to know
ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a specific type of fibrosing interstitial pneumonia of unknown cause. It is usually chronic and progressive, tends to affect mainly adults over age 60, has a predilection for men, and is often fatal. The condition is still underappreciated by pulmonologists and primary care physicians. This article attempts to close that information gap by reviewing the natural course of IPF and presenting an algorithmic approach to diagnosis and treatment based on evidence-based international guidelines. New treatment options are briefly discussed, to raise awareness of new medications that target pulmonary fibrosis.
KEY POINTS
- IPF is characterized by a pattern of usual interstitial pneumonia on imaging and histopathology without another known etiology.
- We recommend early referral to a center specializing in interstitial lung disease to confirm the diagnosis and to initiate appropriate therapy.
- Specialized centers offer advice on prognosis, enrollment in disease registries and clinical trials, and candidacy for lung transplant.
A DIAGNOSTIC ALGORITHM FOR IPF
Given the multitude of interstitial lung diseases, their complexities, and the lack of a gold standard definitive diagnostic test, the diagnosis of IPF can be difficult, requiring the integration of clinical, radiologic, and, if necessary, pathologic findings.
Demographic features
The patient’s demographic features and risk factors dictate the initial clinical suspicion of IPF compared with other interstitial lung diseases. The incidence of IPF increases with age, and IPF is more common in men. A history of smoking is another risk factor.31 A 45-year-old never-smoker is much less likely to have IPF than a 70-year-old former smoker, and a 70-year-old man is more likely to have IPF than a woman of the same age. Thus, the finding of interstitial lung disease in a patient with a demographic profile that is not typical (ie, a younger woman who never smoked) should prompt an exhaustive investigation for another diagnosis such as hypersensitivity pneumonitis or connective tissue disease.
Key elements of the history
After considering the demographic profile and risk factors, the next step in the evaluation is a thorough and accurate medical history. This should include assessment of the severity of dyspnea and cough, signs and symptoms of connective tissue disease (eg, arthralgias, sicca symptoms, Raynaud phenomenon, difficulty swallowing), and gastroesophageal reflux disease, which can be associated with connective tissue disease and, independently, with IPF.
It is also important to identify any environmental exposures that suggest pneumoconiosis or chronic hypersensitivity pneumonitis. The most common risk factors for hypersensitivity pneumonitis are birds and bird feathers, molds, fungi, hot tub use, and some industrial chemicals.32
A medication history is important. Many medications are associated with interstitial lung disease, but amiodarone, bleomycin, methotrexate, and nitrofurantoin are among the common offenders.33
A thorough family history is necessary, as there are familial forms of IPF.
Focus of the physical examination
The physical examination must include careful auscultation for rales. While rales are not specific for IPF, they are the most common pulmonary abnormality. Detailed skin, musculoskeletal, and cardiovascular examinations are also important to evaluate for rheumatologic signs, clubbing, or evidence of heart failure or pulmonary hypertension.
Laboratory tests
Laboratory testing should include a serologic autoantibody panel to evaluate for connective tissue diseases that can manifest as interstitial lung disease, including rheumatoid arthritis, dermatopolymyositis, scleroderma, Sjögren syndrome, and undifferentiated or mixed connective tissue disease. Typical preliminary laboratory tests are antinuclear antibody, rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein. Others may include anticyclic citrullinated peptide (anti-CCP), anti-Scl-70, anti-RNP, anti-SS-A, anti-SS-B, and anti-Jo-1.16 The breadth of the panel should depend on patient demographics and findings in the history or physical examination that increase or decrease the likelihood of a connective tissue disease.
Lung function testing
Assessing the patient’s pulmonary physiology should include spirometry, DLCO, and body plethysmography (lung volumes). In most cases, IPF manifests with restrictive physiology. Once restrictive physiology is confirmed with a low total lung capacity, FVC testing can be used as a longitudinal surrogate, as it is less expensive and easier for the patient to perform. In general, a lower total lung capacity or FVC indicates more severe impairment.
The DLCO serves as another marker of severity but is less reliable due to baseline variability and difficulties performing the maneuver.
A 6-minute walk test is another crucial physiologic assessment tool that can quantify exertional hypoxemia and functional status (ie, distance walked), and can assist in prognosis.
Imaging
Most patients undergo chest radiography in the workup for undiagnosed dyspnea. However, chest radiography is not adequate to formulate an accurate diagnosis in suspected interstitial lung disease, and a normal radiograph cannot exclude changes that might reflect early phases of the disease. As the disease progresses, the plain radiograph can show reticulonodular opacities and honeycombing in the peripheral and lower lung zones (Figure 3).34
The decision whether to order HRCT in the workup for a patient who has dyspnea and a normal chest radiograph is challenging. We recommend cross-sectional imaging when physiologic testing shows restriction or low DLCO, or when there is a high index of suspicion for underlying lung disease as the cause of symptoms.
Expert consultation can aid with this decision, especially when the underlying cause of dyspnea remains unclear after initial studies have been completed. Otherwise, HRCT is an essential test in the evaluation of interstitial lung disease.
Bronchoscopy’s role controversial
If the pattern on HRCT is nondiagnostic, then surgical biopsy is necessary, and the diagnosis of IPF requires a histologic pattern of UIP as described above.16,35
Although bronchoscopy can be valuable if an alternative diagnosis such as sarcoidosis or chronic hypersensitivity pneumonitis is suspected, the role of bronchoscopic biopsy in the workup of IPF is controversial. The patchy nature of UIP does not lend itself to the relatively small biopsy samples obtained through bronchoscopy.36,37
Surgical biopsy options
The favored biopsy approach is surgical, using either an open or a video-assisted thoracoscopic technique. The latter is preferred as it is less invasive, requires a shorter length of hospital stay, and allows a faster recovery.38 Bronchoscopic cryobiopsy, currently under investigation, is a potentially valuable tool whose role in diagnosing IPF is evolving.
Frequently, neither HRCT nor surgical lung biopsy demonstrates UIP, making the definitive diagnosis of IPF difficult. Moreover, some patients with nondiagnostic HRCT results are unable to tolerate surgical lung biopsy because of severely impaired lung function or other comorbidities.
The role of multidisciplinary discussions
When surgical lung biopsy is not possible, current practice at leading centers uses a multidisciplinary approach to allow for a confident diagnosis.30,39 Discussions take place between pulmonologists, pathologists, radiologists, and other specialists to collectively consider all aspects of a case before rendering a consensus opinion on the diagnosis and the management plan. If the discussion leads to a consensus diagnosis of IPF, then the patient’s clinician can move forward with treatment options. If not, the group can recommend further workup or alternative diagnoses and treatment regimens. The multidisciplinary group is also well positioned to consider the relative risks and benefits of moving forward with surgical lung biopsy for individual patients.
This approach illustrates the importance of referring these patients to centers of excellence in diagnosing and managing complex cases of interstitial lung disease, including IPF.40
