Discussion
Juvenile CTD is accompanied by high morbidity and mortality and can disturb any organs. Yet, ILD is an uncommon but it is one of the most significant complication of CTD 6,35. The serum KL-6 level is secreted by type II alveolar epithelium and elevated with lung tissue regeneration 36-38. KL-6, which is a sensitive and specific marker for the development of ILD34,39-41. As a result of this solid review, our study aims to evaluate the correlation between serum KL-6 levels with both presence of interstitial lung disease (ILD) and its severity in connective tissue diseased children, directing to early detection and better management of interstitial lung disease in CTD children.
Regarding to KL-6 serum level and its relationship with severity of ILD and other measured parameters, our study concluded that the KL-6 levels were increased in the CTD with ILD patients compared to the CTD without ILD and control groups. At the cut-off value of serum KL-6 to distinguish ILD was 63.4 U/ml, with sensitivity of 95.2%, specificity of 89.7%, positive predictive value of 83.26% and negative predictive value of 97.2%. Similar results were reported by Oguz et al. who detected increased KL-6 levels in CTD with ILD patients than patients without ILD and control groups 6 . In the same way, Fathi et al. reported that the KL-6 levels were increase in 12 patients with polymyositis and DM + ILD 42 . Furthermore, Fukaya et al. presented that the KL-6 level is a marker of ILD in CTD, and also indicate disease activation and follow up43. In that study, no correlation was found between disease duration and KL-6 level, which disagree with our study, as we concluded that there is a significant direct correlation between disease period and KL-6 level.
Regarding to associations between serum levels of KL-6 and spirometry (PFT) parameters, our study showed that there is a significant inverse correlation between KL-6 serum level and pulmonary function parameters (predicted FEV1 and FVC%) Matching to our study, the PFT is used to detect respiratory complication in CTD studies carried out by44-46. Although it is a non-invasive test that can be repeated easily, it requires collaboration from the patient and is difficult to do in younger children. In a study of polymyositis and DM patients, an inverse correlation was found between KL-6 serum level and PFT parameters in patients with ILD 42.moreover, Hu et al. stated that polymyositis and DM patients with ILD had a greater KL-6 levels than patients without ILD, and they also found that the KL-6 levels were significantly inversely correlated with FEV1 and FVC% 38. Furthermore, Cao et al. proved that the elevated serum KL-6 correlates with the worsening of lung function of SSC–ILD patients 47.
It is challenging to identify strong correlation between ILD and different CTD types because of the small number of ILD patients. Also, the study sample was diverse, and we did not assess the active CTD exacerbation. Furthermore, we did not do HRCT to asymptomatic patients to reduce radiation exposure and thus asymptomatic ILD patients might be skipped. This lowers the power of our work.