Risk factors associated with the development of interstitial lung abnormalities

Background Around 8–10% of individuals over 50 years, present interstitial lung abnormalities (ILA), but their risk factors are uncertain.

Methods From 817 individuals recruited in our “Lung Aging Program”, 80 (9.7%) showed ILA and were compared with 564 individuals of the same cohort with normal HRCT to evaluate demographic and functional differences, and with 80 individuals, randomly selected from the same cohort for biomarkers. We evaluated MUC5B (rs35705950) variant, telomere length, and serum levels of matrix metalloproteinases (MMP)-1, -2, -3, -7, -8, -9, -12, -13, interleukin (IL)-6, surfactant protein (SP)-D, alpha-Klotho and resistin.

Results Individuals with ILA were usually males (p<0.005), older than controls (<0.0001), smokers (p=0.01), with greater frequency of MUC5B rs35705950 (OR 3.5; CI 95% 1.29–9.44, p=0.01), and reduced DL_CO and oxygen saturation. Resistin, IL-6, SP-D, MMP-1, MMP-7, and MMP-13 were significantly increased in individuals with ILA. Resistin (12±5 ng mL⁻¹ versus 9±4 ng·mL⁻¹; p=0.0005) and MMP-13 (357±143 versus 298±116, p=0.004 pg·mL⁻¹), were the most increased biomarkers. On follow-up (24±18 months), 18 individuals showed progression which was associated with gastroesophageal reflux disease (OR 4.1 CI 95% 1.2–12.9, p=0.02), and in females with diabetes mellitus (OR 5.3, CI 95% 1.03–27.4, p=0.01).

Conclusions Around 10% of asymptomatic respiratory individuals enrolled in our lung aging program show interstitial lung abnormalities. Increased serum concentrations of pro-inflammatory molecules and MMPs are associated with ILA.