Aim To develop and to validate novel equations To develop and to validate novel equations for ELA from varied anthropometric data and for ELA from varied anthropometric data and FEVFEV11..

Novel regression equations predicting lung age for Mediterranean populationBen Saad H1,2, Selmi H2, Hadj Mabrouk K2, Maatoug C2, Rouatbi S1

1Department of Physiology and Functional Explorations. Farhat HACHED Hospital. 2Functional Exploration Laboratory. Occupational Medicine Group of Sousse. Tunisia.

Methods

Results

Conclusion

Design: Design: cross sectional study.cross sectional study.Subjects:Subjects: Group I (equation group): Group I (equation group): healthy never-smokers aged 19-90 Yrs with normal spirometry (176 ♂, 364 ♀). Group II (healthy subject’s validation Group II (healthy subject’s validation group): group): healthy never-smokers aged 22-89 Yrs with normal spirometry (20 ♂; 41 ♀). Group III (patients’ validation group): COPD patients aged 19-80 Yrs (65 ♂; 26 ♀): post-bronchodilator FEV1/FVC < 0.70.

Collected data: Collected data: dependent variable (CLA), independent variables [sex, age, weight, height, BMI, FVC, FEV1, PEF, MMEF, FEFx, FEV1/FVC] and ELAs from the published studies.Spirometry function tests Spirometry function tests according ATS/ERS-2005.ELA influencing factors T-tests: associations CLA and categorical variables (sex). Pearson product-moment correlation coefficients: CLA and continuous measures.ELA simplified reference equations: ELA (Yrs) = a0 + a1 x Sex + a2 x Height + a03 x Weight + a4 x BMI + a5 x BSA + a6 x FEV1

Upper and lower limit of normal (ULN, LLN): calculated.

Rational

Novel regression equations allowing prediction of Novel regression equations allowing prediction of reference value of ELA and normal limits of difference reference value of ELA and normal limits of difference between ELA and CLA age were elaborated in both between ELA and CLA age were elaborated in both sexes for Tunisian adult’s population. sexes for Tunisian adult’s population. In additional groups of adult-healthy or adult-patients In additional groups of adult-healthy or adult-patients prospectively assessed, our reference equations yielded prospectively assessed, our reference equations yielded satisfactory predictions.satisfactory predictions.

It have been demonstrated that published It have been demonstrated that published reference equations predicting estimated lung reference equations predicting estimated lung age (ELA) (age (ELA) (Morris and TempleMorris and Temple19851985, Newbury, Newbury20102010, ,

HansenHansen20102010, Yamaguchi, Yamaguchi20122012) didn’t reliably predict ) didn’t reliably predict

chronological lung age (CLA) data in Tunisian chronological lung age (CLA) data in Tunisian healthy adults representing a sample of a healthy adults representing a sample of a Mediterranean population. Mediterranean population.

AbbreviationsFEFx: forced expiratory flow when x% of FVC has been exhaled. FEV1: first second forced expiratory volume. FVC: forced vital capacity. LLN: lower-limit-of-normal. MMEF: maximal mid-expiratory flow. PEF: peak expiratory flow. BMI: body mass index.

Fig 1. Comparison of ELA determined from the retained Tunisian reference equations with CLA in group II. r2: determination coefficient; r: correlation coefficient; p: probability; n=number of subjects. Fig A: male. Fig B: female. : regression line. : identity line.

Validation of prediction equations: CLAs are compared with ELAs: i) Wilcoxon matched pairs test (ELA vs. CLA of groups I-III). ii) Bland and Altman (group II)..iii) Scatterplots and paired T-tests: CLA vs. ELA of group II. iv) One-way ANOVA and Turkey test: .difference between the four COPD grades.

ELA simplified reference equationsELA simplified reference equations ♀: ELA (Yr) = 64.64 - 8.00xFEV1 (L) - 0.17xBMI (kg/m2) + 8.82xHeight (m); r2: 0.38; ULN/LLN= 14.77 Yrs. ♂: ELA (Yr) = 42.85 - 20.74xFEV1 (L)+ 47.41xBSA (m2) - 0.62xBMI (kg/m2); r2: 0.56; ULN/LLN= 16.0 Yrs.

Anthropometric and spirometric data of groups I-III. Group I:

equation group Group II:

validation group Group III:

COPD patients ♂(n=176) ♀(n=364) ♂(n=20) ♀(n=21) ♂(n=65) ♀(n=26)

CLA (Yr)

45±15 50±11a 43±17 42±13b 62±9b 57±15b ELA (Yr)

45±12 50±7a 40±14 46±8b 81±12bc 66±3bc Height (m)

1.66±0.08 1.63±0.11a 1.70±0.10 1.65±0.12 1.70±0.06b 1.53±0.06b

Weight (kg)

74±12 73±12 70±9 70±12 71±13 63±18b

BMI (kg/m2)

27±4 27±3a 26±3 26±4b 25±4b 27±7

FEV1

(%) 97±11 114±21a 102±16 127±21a,b

52±19b 41±17b

Data are mean±SD. ap <0.05 (Student-test for the same sex-group). bp <0.05 (Student-test for sex-group II and III vs. group I). cp <0.05 (non parametric-test for each group): ELA vs. CLA for male, female and the total sample.

Validation of the retained reference equationsValidation of the retained reference equations ELA in group II (fig 1): males and females means±SD (CLA-ELA) weren’t significant (respectively, 3±13 vs. -3±9 Yrs). ELA group III (fig 2): (CLA-ELA) averaged -1.84 Yrs in COPD-grade I, +13.34 Yrs in COPD-grade II, +21.68 Yrs in COPD-grade III, or +26.42 Yrs in COPD-grade IV.

Fig 2. CLA minus ELA in COPD patients.

: mean. : 95% CI. Dotted line: average ULN for (CLA-ELA) (+16 Yrs). P < 0.05: one-way ANOVA (and multiple comparison of the Turkey test) between the 4 COPD grades.a: larger than grade I.b: larger than grade II.c: larger than grade III.