Markers of early disease and prognosis in COPD

COPD is a complex disease with multiple pathological components, which we unfortunately tend to ignore when spirometry is used as the only method to evaluate the disorder. Additional measures are needed to allow a more complete and clinically relevant assessment of COPD. The earliest potential risk factors of disease in COPD are variations in the genetic background. Genetic variations are present from conception and can determine lifelong changes in enzyme activities and protein concentrations. In contrast, measurements in blood, sputum, exhaled breath, broncho-alveolar lavage, and lung biopsies may vary substantially over time. This review explores potential markers of early disease and prognosis in COPD by examining genetic markers in the α1-antitrypsin, cystic fibrosis transmembrane conductance regulator (CFTR), and MBL-2 genes, and by examining the biochemical markers fibrinogen and C-reactive protein (CRP), which correlate with degree of pulmonary inflammation during stable conditions of COPD. Chronic lung inflammation appears to contribute to the pathogenesis of COPD, and markers of this process have promising predictive value in COPD. To implement markers for COPD in clinical practice, besides those already established for the α1-antitrypsin gene, further research and validation studies are needed

Extreme Lipoprotein(a) Levels and Improved Cardiovascular Risk Prediction

ObjectivesThe study tested whether extreme lipoprotein(a) levels and/or corresponding LPA risk genotypes improve myocardial infarction (MI) and coronary heart disease (CHD) risk prediction beyond conventional risk factors.BackgroundElevated lipoprotein(a) levels cause MI and CHD. Levels are primarily determined by variation in the LPA gene.MethodsWe followed 8,720 Danish participants in a general population study from 1991 to 1994 through 2011 without losses to follow-up. During this period, 730 and 1,683 first-time MI and CHD events occurred. Using predefined cutpoints for extreme lipoprotein(a) levels and/or corresponding LPA risk genotypes (kringle IV type 2 [KIV-2]) repeat polymorphism, rs3798220, and rs10455872 single nucleotide polymorphisms), we calculated net reclassification indices from <10% to 10% to 19.9% to ≥20% absolute 10-year MI and CHD risk.ResultsFor individuals with lipoprotein(a) levels ≥80th percentile (≥47 mg/dl), 23% (p < 0.001) of MI events and 12% (p < 0.001) of CHD events were reclassified correctly, while no events were reclassified incorrectly for either endpoint. As some incorrect reclassification of individuals with no events occurred, addition of lipoprotein(a) levels ≥80th percentile overall yielded net reclassification indices of +16% (95% confidence interval: 8% to 24%) and +3% (−1% to 8%) for MI and CHD, respectively. Corresponding net reclassification indices for number of KIV-2 repeats ≤21st percentile were +12% (5% to 19%) and +4% (0% to 8%), for rs3798220 carrier status +15% (−14% to 44%) and +10% (−10% to 30%), and for rs10455872 carrier status +16% (6% to 26%) and +2% (−1% to 6%). Considering only individuals at 10% to 19.9% absolute 10-year MI and CHD risk, addition of extreme lipoprotein(a) levels or corresponding LPA risk genotypes improved risk prediction even further.ConclusionsExtreme lipoprotein(a) levels or corresponding LPA KIV-2/rs10455872 risk genotypes substantially improved MI and CHD risk prediction

A Population-based Study of Morbidity and Mortality in Mannose-binding Lectin Deficiency

Reduced levels of wild-type mannose-binding lectin (MBL) may increase susceptibility for infection, other common diseases, and death. We investigated associations between MBL deficiency and risk of infection, other common diseases, and death during 24, 24, and 8 yr of follow-up, respectively. We genotyped 9,245 individuals from the adult Danish population for three MBL deficiency alleles, B, C, and D, as opposed to the normal noncarrier A allele. Hospitalization incidence per 10,000 person · yr was 644 in noncarriers compared with 631 in heterozygotes (log-rank: P = 0.39) and 658 in deficiency homozygotes (P = 0.53). Death incidence per 10,000 person · yr was 235 in noncarriers compared with 244 in heterozygotes (P = 0.44) and 274 in deficiency homozygotes (P = 0.12). After stratification by specific cause of hospitalization or death, only hospitalization from cardiovascular disorders was increased in deficiency homozygotes versus noncarriers (P = 0.02). When retested in two case control studies, this association could not be confirmed. Incidence of hospitalization or death from infections or other serious common disorders did not differ between deficiency homozygotes and noncarriers. In conclusion, in this large study in an ethnically homogenous Caucasian population, there was no evidence for significant differences in infectious disease or mortality in MBL-deficient individuals versus controls. Our results suggest that MBL deficiency is not a major risk factor for morbidity or death in the adult Caucasian population