We did not confirm by genotyping that low MBL concentrations were the result of variant alleles. Approximately 30% and 4%-8% of the normal population have heterozygous or homozygous genetic mutations, respectively, associated with low MBL concentrations. 35 Although MBL concentrations are well correlated with genotypes, (eg, MBL concentrations , 50 ng/mL are 100% sensitive and 83% specific for variant exon-1 polymorphisms 43 ) subjects with wild-type MBL genes may still have low concentrations of MBL, 35 and MBL concentrations may vary as much as 10-fold in patients with identical genotypes for all of the MBL variants described to date. 38 Accordingly, assessing relationships between MBL concentrations and AECOPDs is likely to be a more sensitive approach than genotyping. 21 Similarly, we did not assess MBL function using a complement deposition assay. Bouwman et al 47 and Eisen 48 suggested that while MBL function was a better way of defining MBL deficiency than determining MBL concentrations, assessing MBL concentrations was "most appropriate" for defining MBL deficiency in studies seeking associations with infections. Differences between MBL binding and complement activation may vary depending on the method of assessment, 49 and MBL concentrations from 500 ng/mL to 1000 ng/mL are associated with decreases in function by up to 90%. 9 While we saw no association between MBL deficiency and AECOPDs, MBL deficiency could still be associated with AECOPDs that result from infection with one or more specific pathogens if the frequency with which these specific pathogens affected our subjects was too low to discern the association. However, we think this possibility is unlikely, because the two studies documenting the association between MBL deficiency and AECOPDs found an association with AECOPDs that were not otherwise defined by cause or potential infecting organism. 30, 32 In addition, Lin et al 32 found no difference in the distribution of pathogens in those subjects with AECOPD and without MBL-deficient genotypes.