Question: I understand that there is no evidence supporting the use of corticosteroid and cyclophosphamide therapy for patients with confirmed IPF. However, in some cases the diagnosis is not definitive and therefore this therapy might be beneficial for the patient. What are the critical diagnostic findings that should guide the decision on immunosuppressive therapy when IPF is suspected but not confirmed?

Answer: The lack of evidence for efficacy of corticosteroids and additional immunosuppression in IPF suggests that this approach should not be taken in cases of confirmed IPF. The IPFnet is conducting a trial of prednisone/azathioprine/N-acetyl cysteine vs N-acetyl cysteine vs Placebo, which may furnish indirect evidence for prednisone/azathioprine efficacy.1 Your question is about other diseases that present like IPF that might be appropriately treated with immunosuppressive therapy.

 

This question has to be divided into a few parts:

  • How do we recognize an autoimmune disease?
  • Is immunosuppression effective for autoimmune disease?
  • How long should immunosuppression be tried?

Usually a diagnosis of indefinite IPF results from an "atypical" CT scan without evidence of honeycombing. In the studies that looked at the utility of HRCT for definitive diagnosis, NSIP was difficult to distinguish from IPF. Kinder et al proposed that a positive autoantibody test in a patient with pulmonary symptoms suggests Undifferentiated Connective Tissue Disease or autoimmune disorder.2,3,4 They found that these cases mostly were NSIP. This type of patient would be a candidate for immunosuppressive therapy. These patients should be treated cautiously with immunosuppression because of the side effects. Positive biopsy evidence and high autoantibody titers are suggestive of autoimmunity, where immunosuppression could be appropriate. There should be confident diagnosis of autoimmune disease to proceed with this course. As with IPF, the diagnosis of autoimmune diseases is not trivial. Regional ILD centers are sources of expertise that should be utilized for difficult cases.

In the largest review of NSIP cases by an ATS project group the impact of treatment on overall survivorship was deemed to be "very good." Thus, steroids and immunosuppression is a reasonable option for patients with NSIP.5

Because of the side effects of immunosuppressive therapy, it is important to limit the exposure. This is especially true if the treatment is not proving efficacious. I compare my patients' PFTs at baseline and at 3-6 months of treatment. If there are not appreciable improvements, I withdraw therapy. If the PFTs improve, continuation of has to be guided by balancing the risks and benefits for the individual patient.

  1. Noth I, Martinez F. Recent advances in idiopathic pulmonary fibrosis. Chest. 2007;132:637-650.
  2. Hunninghake GW, Lynch DA, Galvin JR, et al. Radiologic findings are strongly associated with a pathologic diagnosis of usual interstitial pneumonia. Chest. 2003;124:1215-1223.
  3. Raghu G, Mageto YN, Lockhart D, Schmidt RA, Wood DE, Godwin JD. The accuracy of the clinical diagnosis of new-onset idiopathic pulmonary fibrosis and other interstitial lung disease. Chest. 1999;116:1168-1174.
  4. Kinder B, et al. Idiopathic nonspecific interstitial pneumonia: lung manifestation of undifferentiated connective tissue disease? Am J Respir Crit Care Med. 2007;176:691-697.
  5. Travis WD, Hunninghake GW, King TE Jr, et al. Idiopathic nonspecific interstitial pneumonia: report of an American Thoracic Society project. Am J Respir Crit Care Med. 2008;177:1338-1347.