DISCUSSION
In this study the change in lung density and volume due to pulmonary
fibrosis in patients with SSc evaluated by a soft-ware aided image
segmentation method was investigated. According to the study hypothesis,
fibrosis of lung tissue should lead to increased lung density and
reduced lung volume due to decreased ventilation [15]. Consistent
with this hypothesis, it was shown that right and left lung densities
were higher in SSc patients with signs of fibrosis than SSc patients
without pulmonary fibrosis and healthy controls.
Although parenchymal changes related to fibrosis were detected in
approximately 80-100% of SSc patients in early autopsy studies
[2,16], it is known that lung involvement in SSc varies between
40-60% when assessed by HRCT studies [17-19]. In line with the
literature, it was expected that lung densities would be decreased in
the patients without fibrosis-related morphological changes on HRCT
compared to healthy subjects indicating sub-clinical and
sub-radiological lung involvement. However, lung densities showed no
difference between the patients without signs of fibrosis and controls.
It hs previously been shown that PF is closely related to
anti-topoisomerase antibody positivity and diffuse cutaneous
involvement, and thus patients without fibrosis-related morphological
changes on HRCT were analyzed after subgrouping them into limited and
diffuse cutaneous sub-types [15,18,20]. Our results showed that in
dcSSc patients, even if there were no signs of interstitial lung disease
(ILD) in HRCT, lung densities were higher than those of lcSSc and
control patients. This result suggested that early changes in lung
density may appear before the architectural distortion on HRCT in dcSSc
compared to lcSSc patients. Numerous studies have confirmed that
patients with lcSSc or dcSSc have distinct autoantibody profiles,
patterns of organ involvements, progression, and outcomes [21-22].
There is still controversy whether the two subtypes of SSc represent
truly distinct diseases or merely different extremes of one disease
spectrum [23]. We suggest that the two subtypes differ in terms of
lung density in radiologically non-apparent disease, although the
clinical significance of this is unknown.
The annual follow-up HRCT scans of the 56 patients without any
morphological signs of fibrosis on HRCT were evaluated and it was found
that 16 (28.6%) of the patients developed abnormal imaging after a mean
of ten years from baseline scans. It was shown that the baseline right
and left lung densities were significantly lower in the future PF
developers than the non-developers. However, there is little evidence to
support the predictive value of decreased lung density for PF
development in the future. Therefore its role as a parameter in
assessing and monitoring newly diagnosed patients should be investigated
in larger cohorts. Considering the heterogeneity of systemic
sclerosis-associated interstitial lung disease (SSc-ILD), the potential
absence of symptoms in early or mild disease, and the potential impact
of ILD on outcomes in patients with SSc, our results may contribute to
prediction models in SSc-ILD [24].
There was a weak correlation between lung volumes and left lung density
and both FVC and DLCO in patients without PF. However, the association
became stronger in PF between the densities and left lung volume and
both FVC and DLCO. Based on our results, the gradual development of a
relationship with the effect of fibrosis-related changes in the lung
parenchyma was evident.
Interestingly, the expected decrease in lung volumes due to fibrosis
were inconsistent in some subgroup analyses. We believe that this
variability may be due to a change in compensatory capacity of the lungs
in response to any volume-decreasing pathology. Thus, due to this
possible confounder, the main focus of the study was lung density and we
believe that use of lung volume as a measurement parameter may be
misleading.
One of the most important limitations of our study was that follow-up
HRCT scans were not performed in all patients at regular intervals due
to the retrospective design. Thus, we refrain from making precise
comments about the time to the onset of PF, especially in patients with
dcSSc. The small sample size was another limitation, leading to
unreliable statistical analysis in some of the subgroup comparisons.