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Idiopathic Pulmonary Fibrosis: Prognostic Value of Changes in Physiology and Six-Minute-Walk Test

Flaherty KR, Andrei AC, Murray S, Fraley C, Colby TV, Travis WD, Lama V, Kazerooni EA, Gross BH, Toews GB, Martinez FJ. Am J Respir Crit Care Med. 2006:174;803-809.

Discussion

• Predicting survival in patients with idiopathic pulmonary fibrosis (IPF) remains a challenge for clinicians.
• Recent publications have suggested a role for serial changes in pulmonary function and the presence of baseline desaturation on 6-minute walk testing (6MWT),^1-4 but little is known about how to use these measures in combination.
• The authors of this paper utilize a large cohort of well-described patients with idiopathic pulmonary fibrosis to investigate the prognostic value of the 6MWT in relation to changes in FVC and DL_CO.

Study Design:

• One hundred ninety-seven patients with IPF were retrospectively identified.
• Baseline and 6-month follow-up values were determined:
• Pulmonary function tests (FVC, DL_CO)
• 6-minute walk distance
• Lowest saturation on 6MWT
• Desaturation area (defined as the total area above the 6MWT saturation curve)
• Kaplan-Meier and regression analyses were performed to assess the predictive value of individual and multiple combinations of measures for survival.
• Additional analyses were stratified by the presence or absence of desaturation (as defined by a lowest oxygen saturation of ≤ 88%).

Results:

• Although baseline 6-minute walk distance was predictive of survival (HR 0.94 per 100-foot increase, P = 0.005), a more powerful baseline predictor of survival was desaturation on 6MWT, as defined by either an increase in desaturation area (HR 1.33, P = 0.007, per 10-point increase) or desaturation ≤ 88% (HR not given, P = 0.006).
• Multivariate modeling of subgroups defined by the presence or absence of desaturation (oxygen saturation of ≤ 88% on 6MWT) demonstrated differing predictive values for 6-month changes in clinical variables:
• No desaturation on 6MWT: 10% decline in FVC, 15% decline in diffusing capacity, > 200-foot decline in 6-minute walk distance, and worsened saturation on 6-minute walk test were predictive of survival
• Desaturation on 6MWT: Only 15% decline in diffusing capacity was predictive of survival
• There was significant correlation between certain predictor variables (eg, diffusing capacity and desaturation area).

Implications/Recommendations:

• Baseline 6MWT desaturation is important for prognosis in patients with IPF.
• Desaturation is a more powerful baseline predictor than distance walked or diffusion capacity.
• More sophisticated measurements of desaturation (such as the desaturation area) may have clinical utility.
• These data confirm the predictive power of change in FVC and diffusing capacity over time. The finding that the predictive value of these changes depends on the presence or absence of desaturation is provocative and should be examined in additional cohorts.
• Current clinical measures are poor predictors of survival in IPF and predicting survival in IPF remains difficult.
• Clinicians should discuss the prognostic implications of these tests with patients only in general terms.
• Clinicians should utilize baseline diffusing capacity and desaturation (as defined by both saturation ≤ 88% and desaturation area) as well as serial FVC (10% decline) and DL_CO (15% decline) at 6-month intervals.
• Continued research into the pathobiology and natural history of this disease may identify additional predictors (eg, pulmonary hypertension) and help refine our approach to prognosis.

Reference

1. Collard HR, King TE Jr, Bartelson BB, Vourlekis JS, Schwarz MI, Brown KK. Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2003;168:538-542.
2. Flaherty KR, Mumford JA, Murray S, et al. Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia. Am J Respir Crit Care Med. 2003;168:543-548.
3. Lama VN, Flaherty KR, Toews GB, et al. Prognostic value of desaturation during a 6-minute walk test in idiopathic interstitial pneumonia. Am J Respir Crit Care Med. 2003;168:1084-1090.
4. Latsi PI, du Bois RM, Nicholson AG, et al. Fibrotic idiopathic interstitial pneumonia: the prognostic value of longitudinal functional trends. Am J Respir Crit Care Med. 2003;168:531-537.

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