title: The Prognostic Role of Ventilatory Inefficiency and Exercise Capacity in Idiopathic Pulmonary Fibrosis.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal interstitial lung disease associated with poor prognosis and limited effective treatment options. Reliable predictors of outcome in daily clinical practice are needed to determine high-risk patients for urgent lung transplantation referral. This study aimed to identify practical prognostic predictors of mortality using cardiopulmonary exercise testing (CPET) in IPF subjects.
  
  
  METHODS
  Thirty-four subjects with IPF (22 men and 12 women), median age 68 (range 50-81) y were prospectively studied. At baseline, all subjects were assessed with CPET and were followed up for 40 months from baseline. Receiver operating characteristic curve analysis was conducted to determine cut-off points of CPET variables for mortality, Cox regression analysis for survival using a log-rank test, and hazard ratio for death using a Wald test.
  
  
  RESULTS
  Peak work rate <62 watts (P = .005), peak V̇O2 ≤13.8 mL/kg/min (P = .031), tidal volume reserve ≤0.48 L/breath (P = .010), minute ventilation to carbon dioxide (V̇E)/V̇CO2 ) ratio at the anaerobic threshold >34 (P = .02), and V̇E)/V̇O2 nadir >34 (P = .002) were detected as cut-off points associated with mortality. Non-survivor subjects were characterized by higher dyspnea levels, the presence of pulmonary hypertension assessed by echocardiography, pronounced inefficient ventilatory pattern, lower exercise capacity, and more severe desaturation during physical exertion. By the end of the study, 11 subjects (7 women and 4 men) died. Overall mean survival was 60%, 33.7 months (95% CI 30.2-37.2).
  
  
  CONCLUSIONS
  This study provides simple, practical, and novel cut-off points for CPET as predictors of prognosis to identify high-risk IPF subjects. Impairment in exercise capacity and abnormal ventilatory responses during CPET were associated with poorer survival in IPF subjects. The findings suggest considering the use of CPET for IPF risk stratification and prediction of prognosis. (ClinicalTrials.gov registration NCT01499745.).
authors.affiliation: Pulmonary Institute, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel. Research Center in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sport, University of Porto, Porto, Portugal. baruch.v1981@gmail.com.
authors.forename: Baruch
authors.initials: B
authors.lastname: Vainshelboim
authors.affiliation: Research Center in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sport, University of Porto, Porto, Portugal.
authors.forename: Jose
authors.initials: J
authors.lastname: Oliveira
authors.affiliation: Pulmonary Institute, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Benjamin Daniel
authors.initials: BD
authors.lastname: Fox
authors.affiliation: Pulmonary Institute, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Mordechai Reuven
authors.initials: MR
authors.lastname: Kramer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015308:Anaerobic Threshold; D004417:Dyspnea / Q000209:etiology / Q000503:physiopathology; D005080:Exercise Test / Q000379:methods / Q000592:standards*; D017079:Exercise Tolerance / Q000502:physiology; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000150:complications / Q000401:mortality* / Q000503:physiopathology; D008176:Lung Volume Measurements; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000502:physiology; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012123:Pulmonary Ventilation; D012372:ROC Curve; D012015:Reference Standards; D012044:Regression Analysis; D018570:Risk Assessment / Q000379:methods / Q000592:standards*; D015996:Survival Rate
keywords: cardiopulmonary exercise testing; exercise intolerance; prognostic predictors; survival; ventilatory response