Question: What is the role of genetic testing in patients with IPF?

Answer: There have been some recent discoveries in patients with familial pulmonary fibrosis, a condition with varying phenotype and defined by the presence of pulmonary fibrosis in two or more family members. Mutations in genes related to telomerase function have been identified in families manifesting clinical and histopathological evidence of IPF (Tsakiri et al. Proc Natl Acad Sci USA. 2007;104:7552, Armanios et al. N Engl J Med. 2007;356:1317). Telomerase length is important to cellular proliferation and response to injury. Mutations in surfactant protein C have also been associated with ILD (Thomas et al. Am J Respir Crit Care. 2002;165:1322). Given these findings, many patients and their family members are understandably interested in finding out whether or not they carry similar mutations. In my opinion, however, genetic testing in ILD is not yet ready for clinical use. For patients, we have no idea how the presence of one of these mutations should affect prognosis and management. For family members or other unaffected individuals, we do not know the risk these mutations confer for developing ILD later in life. While there is arguably inherent value for some patients in knowing whether or not they may carry a mutation known to be associated with ILD, our inability to translate this knowledge into prognostic or therapeutic recommendations makes the costs associated with such testing (psychological in particular, but also financial) hard to justify.

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Question: What is the role for bronchoscopy in patients with presumed idiopathic pulmonary fibrosis (IPF)?

Answer: There is general consensus (although not universal) that transbronchial biopsy serves little role in the diagnosis of IPF. Although a recent publication suggests otherwise in selected cases (Berbescu et al. Chest. 2006;129:1126), it is generally believed that the accurate diagnosis of IPF (ie, the demonstration of usual interstitial pneumonia pattern on lung biopsy) requires a surgical technique. Bronchoscopy can aid in the clinical diagnosis of IPF, and has been included as one of the major diagnostic criteria, as published by the American Thoracic Society/European Respiratory Society (Am J Respir Crit Care Med. 2000;161:646). It is most useful in reducing the likelihood of alternative diagnoses (eg, chronic eosinophilic pneumonia, hypersensitivity pneumonitis) which would demonstrate striking elevations of particular cell types on the differential cell count of bronchoalveolar lavage fluid. There is some debate about whether or not bronchoscopy and bronchoalveolar lavage should be required for the clinical diagnosis of IPF and many practicing clinicians do not routinely perform this test as part of their diagnostic evaluation (Collard et al. Respir Med. 2007;101:2011).

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Question: How should I follow patients with ILD over time?

Answer: The strongest data exist for serial pulmonary function measurements, in particular forced vital capacity (Flaherty et al. Am J Respir Crit Care Med. 2003;168:543). Additional data exist for dyspnea and diffusion capacity, although the data are not as strong. There are no compelling data for serial high resolution CT scanning. My practice is to follow patients every 6 months (unless clinical events dictate a shorter interval) with an assessment of dyspnea, spirometry, and diffusion capacity measurement. I do not, as a general rule, perform serial CT scanning. There are several metrics for dyspnea; my favorite is the baseline/transitional dyspnea index (Witek and Mahler. Eur Respir J. 2003;21:267) although data using this scale in IPF are limited. The only tested measure is the CRP Dyspnea scale (Watters et al. Am Rev Respir Dis. 1986;133:97); a change of 2 points or greater is prognostic (Collard et al. Am J Respir Crit Care Med. 2003;168:538). Changes in 10% or greater in forced vital capacity and 15% in diffusion capacity are considered significant and prognostic. Stability or improvement in these measures should suggest that the disease is stable and/or the therapy is working. Worsening of these measures should prompt a change in therapy, including evaluation for lung transplantation.

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Question: What alternatives are there to prednisone for the treatment of interstitial lung disease?

Answer: Corticosteroids are still first-line therapy for most forms of interstitial lung disease (ILD), but many patients experience significant morbidity (eg, hyperglycemia, weight gain, agitation, mood disturbance) and require an alternative medication. While the choice varies somewhat based on the diagnosis, a few general comments can be made. There are three drugs that are routinely used in combination with, or in place of, corticosteroids for the treatment of ILD. These are cyclophosphamide, azathioprine, and mycophenolate. All three drugs work to suppress the immune system. There are significant potential toxicities associated with each, and unlike prednisone, regular blood work is required. These medications should be prescribed by a physician expert in the care of ILD.