Primary ciliary dyskinesia (PCD) is an autosomal recessive or X‐linked disorder that results from mutations in one or more genes that encode the structural and functional proteins of motile cilia. Notably, PCD leads to abnormal ciliary function. This in turn obstructs mucociliary clearance, causing recurrent and often chronic infections in the upper and lower respiratory tracts.
Mirror imaging of the internal organs is see in 40% to 50% of patients with PCD. Over time, patients with PCD show structural changes in their lungs, such as bronchiectasis, peribronchial thickening, and mucus plugging. Patients with PCD also show decrease lung function over time, although to a lesser degree than in cystic fibrosis.
Decrease in lung function
Aggressive treatment, such as antibiotics and lung physiotherapy; so may mitigate the decrease in lung function. However, the treatment results are variable, and trends in lung function in PCD patients are often difficult to explain or to predict. Mannose‐binding lectin (MBL) is a serum protein that activates the complement system; hence through the lectin pathway in the innate immune system. The MBL gene name MBL is locate on chromosome.
Three different single point variants in MBL exon have report that give rise to four alleles (A, the normal allele; B, C, and D, mutate alleles that are collectively refer to as O). These MBL variants makes the resulting MBL protein products unstable, easily degrade, and are thought to have shorter half‐lives; so all of which lead to lower serum concentrations of MBL and to reduce function of circulating MBL.
The greatest strength of this study was the relatively large number of patients; so all of whom were diagnose with PCD according to standard guidelines. Further, all patients were follow, monitor, and treat by the same medical team for up to 40 years. Another strength is that there were a large number of longitudinal lung function; so measurements over several years; in fact, one patient had measurements for about 37 years.
Real impact of MBL
The study also had some limitations. Specifically, there is uncertainty regarding its power to detect the real impact of MBL polymorphisms solely from spirometry data. Many other relevant factors, like full observation period; hence with longitudinal ascertainment of individual infection burden, pathogens; hence visit/treatment adherence or numbers of exacerbations were not possible to include in this retrospective study.
Including this information, as well as including complete information about ciliary ultrastructural defects; so pathogenic variants in genes with known association with PCD, and structural lung damage as detect on HRCT, so have greatly improve the study and they highly recommend to prospectively ascertain such data using strict criteria and provide the data to the international registry for PCD.
This study found that Danish patients with PCD with MBL deficiency were diagnose earlier; hence than PCD patients with MBL sufficiency, but there was no difference in the first available spirometry measurements. However, FEV1 decline significantly faster per year in patients with PCD with an MBL genotype associate with MBL deficiency. This suggests that MBL deficiency is a disease modifier in PCD and may, at least in part, explain differences in lung function trends in PCD.