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Kinder BW, Brown KK, McCormack FX, et al. Serum surfactant protein-A is a strong predictor of early mortality in idiopathic pulmonary fibrosis. Chest. 2009;135:1557-1563.

Background:
Predicting survival in patients with idiopathic pulmonary fibrosis (IPF) remains a challenge for clinicians. Recent interest in molecular markers has identified several potential markers that may aid in predicting survival. Surfactant proteins (SP) A and D, type II alveolar cell-derived proteins, are two such markers that have been shown to be associated with lower survival.1,2

Kinder and colleagues3 utilize a large cohort of well-described patients with IPF to test the predictive value of serum SP-A and SP-D levels for mortality at 1 year.

Study Design:
Eighty-two patients with IPF diagnosed by surgical lung biopsy were retrospectively identified.

The following parameters were recorded:

  • Demographics
  • Baseline pulmonary function test values
    • Forced vital capacity
    • Diffusing capacity for carbon monoxide
  • Bronchoalveolar lavage cellular analysis values
  • SP-A levels
  • SP-D levels

Regression analysis was performed to assess the predictive value of individual and multiple combinations of measures for survival at one year. Survival time was calculated from the time of surgical lung biopsy. The area under the receiver operating curve was calculated for various combinations of predictor variables to assess predictive power.

Results:
SP-A, but not SP-D, was associated with decreased survival at 1 year. An increase in SP-A of 49 ng/ml was independently associated with 3.27 times higher one-year mortality risk (95% confidence interval 1.49 to 7.17, P = 0.003). This association was attenuated significantly during subsequent years of follow-up.

The addition of SP-A to regression modeling of one-year mortality improved the area under the receiver operating curve.

Expert Opinion:
This study supports the use of serum SP-A levels at the time of diagnosis as a predictive tool for patients with IPF. Further, this paper suggests that these SP-A levels add prognostic power to commonly measured clinical variables.

There are a few important limitations and qualifications:

  • The focus on one-year mortality is somewhat arbitrary, and it appears the prognostic value at additional timepoints is limited. Results showing the prognostic relevance of SP-A to overall survival time (ie, time to event analysis) would substantiate its value
  • The vast majority of subjects in this study were included in this group's previous publication regarding the prognostic value of serum SP-A in IPF.1 While the current study adds important updates in study design, validation of SP-A's prognostic value in an independent cohort of well-defined IPF patients will be important
  • Serum SP-A measurement remains a research assay that has not been standardized for clinical use

Predicting survival in IPF remains difficult, and looking for novel predictors such as SP-A which may increase our ability to prognosticate is essential. How serum SP-A measurement should fit into the clinical management of patients with IPF remains unclear and should be the focus of additional well-designed studies.

References:

  1. Greene KE, King TE, Kuroki Y, et al. Serum surfactant proteins-A and -D as biomarkers in idiopathic pulmonary fibrosis. Eur Respir J. 2002;19:439-446.
  2. Takahashi H, Fujishima T, Koba H, et al. Serum surfactant proteins A and D as prognostic factors in idiopathic pulmonary fibrosis and their relationship to disease extent. Am J Respir Crit Care Med. 2000;162:1109-1114.
  3. Kinder BW, Brown KK, McCormack FX, et al. Serum surfactant protein-A is a strong predictor of early mortality in idiopathic pulmonary fibrosis. Chest. 2009;135:1557-1563.

Article link:

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