Risk factors associated with the development of interstitial lung abnormalities

Abstract

BackgroundAround 8–10% of individuals over 50 years, present interstitial lung abnormalities (ILA), but their risk factors are uncertain.MethodsFrom 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.ResultsIndividuals 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 DLCO 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−1versus 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).ConclusionsAround 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.

Interstitial lung abnormalities – current knowledge and future directions

“…The prevalence of interstitial lung abnormalities is variable and related to the age of the population examined as well as the frequency of smoking. In general population-based cohorts in which the mean age of participants with ILA was 70 years or older, the prevalence of ILA has been reported between 7 and 10% [ 8 , 16 , 17 ]. Among cohorts of smokers or lung cancer screening cohorts, however, the prevalence of ILA has been found to range from 4 to 20% [ 5 , 8 , 14 , 15 , 18–20 ].…”

“…Cigarette smoking, which is also strongly related to idiopathic pulmonary fibrosis (IPF) risk is associated with ILA, i.e. both smoking at time of examination and amount of smoking over participants’ lifetimes [ 8 ], as well as reduced diffusion capacity for carbon monoxide (DL CO ) and reduced oxygen saturation [ 17 ]. Smokers with ILA also have increased odds of a restrictive lung deficit, decreased lung volumes, and decreased emphysema compared to their peers [ 5 ].…”

“…Potential IPF biomarkers have been found to be related with ILA. Matrix metalloproteases (MMPs) and Galectin-3, markers elevated in IPF patients, are elevated in cohort study participants with ILA [ 17 , 36–39 ]. In addition, among familial interstitial pneumonia patients, those with ILA have been found to have shorter telomeres in peripheral blood than those without ILA [ 40 ].…”

“…In addition, among familial interstitial pneumonia patients, those with ILA have been found to have shorter telomeres in peripheral blood than those without ILA [ 40 ]. Among other possible biomarkers, the adhesion molecule sICAM-1 has been associated with ILA [ 41 ] as well as pro-inflammatory molecule resistin [ 17 ]. Additionally, leptin and the metabolites phosphatidylcholine, phosphatidic acid, betaine aldehyde, phosphatidylethanolamine, and 1-acylglycerophosphocholine [ 42–44 ] have been linked with ILA and certain microRNAs, in particular miR-193a-5p and miR–502–5p, have been shown to be upregulated in ILA and suggested as ILA biomarkers [ 45 ].…”

“…Risk of ILA progression is positively associated with several features such as age, smoking at the time of the study, and the rs35705950 promoter polymorphism of the MUC5B gene [ 50 , 74 ] while the directionality of the relationship of body mass index with ILA progression has varied between studies [ 50 , 74 ]. In addition, exposure to elemental carbon has been associated with ILA progression as well as gastroesophageal reflux [ 17 , 25 ]. In terms of imaging patterns, the definite fibrosis pattern, and both probable and definite UIP patterns are strongly associated with ILA progression [ 14 , 50 ].…”