Tracking Patients With Familial IPF

April 2, 2006

Q:My patient’s family appears to be genetically predisposed topulmonary fibrosis. How should I follow this patient? What earlywarning signs herald the condition, and what diagnostic tests are mostappropriate?

Q:My patient's family appears to be genetically predisposed topulmonary fibrosis. How should I follow this patient? What earlywarning signs herald the condition, and what diagnostic tests are mostappropriate?

A:Many forms of pulmonary fibrosis have a genetic predisposition. Theseinclude the fibroses associated with sarcoidosis, hypersensitivity pneumonitis,some drug reactions, and a few rare disorders, such as tuberous sclerosisand lymphangiomyomatosis.1,2 I will limit my comments here to the largespectrum of pathologic disorders known as idiopathic interstitial pneumonitis/fibrosis--or, more specifically, usual interstitial pneumonitis/fibrosis, whichhas become synonymous with idiopathic pulmonary fibrosis (IPF).

A familial predisposition to IPF has been recognized for more than50 years.3 One study reported on a family in which 8 persons (including twins)in 5 generations had IPF.4 I have cared for such patients myself. Familial IPFtends to affect younger persons and appears to have a worse prognosis thannon-familial IPF.

LET SIGNS AND SYMPTOMS GUIDE YOU
The best way to follow family members of patients with IPF is by closemonitoring of symptoms and periodic use of spirometry. The frequency ofspirometry will depend on the progression of symptoms and the use of therapiessuch as corticosteroids and cytotoxic drugs. Symptoms include chronic,nonproductive cough--either a lingering cough following a presumed viral infectionor an insidious, idiopathic cough of gradual onset. Cough may precedethe telltale "Velcro rales" that indicate pulmonary fibrosis. CT abnormalitiesoften accompany the onset of symptoms and may precede standard chestradiographic findings. Crackles may also precede chest radiographic findings.

Spirometry is far less expensive than imaging and provides evidence offunctional decline. In the initial stages of IPF, the forced vital capacity (FVC)begins to decline, which raises the ratio of forced expiratory volume in 1 secondto FVC from the normal 0.70 to 0.79 to higher values, often more than0.85 or 0.90. This is because the fibrosis restricts lung filling and causes anincrease in elastic recoil.

EARLY DIAGNOSIS IS KEY
Early recognition is important, particularly in smokers. IPF is associatedwith smoking,1 and smoking cessation may help stem disease progression.Early treatment with immunosuppressive drugs appears to be more effectivein early-stage than late-stage disease. However, no agreement exists aboutthe best way to treat IPF, and the prognosis is poor. Studies on interferon-γtherapy are under way.

References:

REFERENCES:1. Verleden GM, du Bois RM, Bouros D, et al. Genetic predisposition and pathogenetic mechanisms of interstitiallung diseases of unknown origin. Eur Respir J Suppl. 2001;32(suppl):17S-29S.
2. McMillan JM. Familial pulmonary fibrosis. Dis Chest. 1950;20:426-436.
3. Bonanni P, Frymoyer JV, Jacon RF. A family study of idiopathic pulmonary fibrosis. Am J Med.1965;39:411-421.
4. Gross TJ, Hunninghake GW. Idiopathic pulmonary fibrosis. N Engl J Med. 2001;345:517-525.