This study demonstrated that esophageal dilation is common in SSc
patients, and that this condition is more frequent in subjects with a
coexisting ILD. Moreover, there is a
clinically significant association between esophageal dilation and HRCT
findings of ILD: esophageal diameter positively
correlates with patient-centred
measures of perceived dyspnea, gastroesophageal symptoms and functional disability, and negatively correlated with DLco. Furthermore, esophageal dilation is more prevalent in subjects with longer disease
duration, is significantly more common in patients with anti-topoisomerase
The mechanisms underlying
SSc-ILD are not yet completely known. Some evidences suggest that both
cell-mediated and humoral immunity play a role in the pathogenesis of ILD (33-37).
A causative relationship between SSc-ILD and other factors, particularly
genetic and environmental, has further been proposed (38-41).
disturbances have also been considered as contributing factors of SSc-ILD
(12,13,15). The changes of esophageal peristalsis and decreased LES pressure
may induce a predisposition to GER (12,13,15,42,43). Many investigators
described how GER can be one of the initiating factors of a variety of
respiratory disorders (e.g., asthma, bronchiectasis, and recurrent acute
pneumonia) (44-51). Microaspirations of gastric content into the lungs are
believed to work as trigger mechanism in inducing pulmonary parenchymal
lesions. Many works have pointed out that GER therapy could potentially improve
symptoms and PFT parameters in these patients (44-46,48,50-52,53-55).
reported the prevalence of esophageal dilation on chest CT scans in SSc
patients. These studies used empirical cut-off values to define esophageal dilation
without regard to normal standards. For example, Bhalla et al. and Pitrez and
colleagues cited a radiographic textbook which defined an
esophageal diameter below the aortic arch >10 mm on axial images as dilated (6,16,55). Takekoshi et al. proposed a cut-off value of
10 mm at the carinal level and 15 mm for maximum diameter (56). Pitrez and
colleagues used the ROC curves to determine the esophageal diameter associated
with esophageal dysmotility, as assessed by radionuclide scintigraphy (16).
They found that an esophageal diameter below the aortic arch >9 mm had the 83.1% sensitivity and the 94.1% specificity for dysfunction.
literature is someway conflicting regarding the association between esophageal
dilation and SSc-ILD.
extrapolated the 9 mm or 10 mm esophageal diameter cut-off point to study the
association with radiographic ILD on HRCT, yielded to conflicting
results: Vonk and colleagues (?10 mm) and Pandey et
al. (?9 mm) did not find a
significant association between esophageal
dilation and ILD (7,18), while. Both 10 mm and 9 mm esophageal diameter cut-off
points seem to have low specificity for the
association with ILD.
Although Pandey and colleagues concluded that there was no association
between esophageal dilatation and ILD, it is possible that the size of the
cohort or the cut-off point of 9 mm may account for the lack of association.
Interestingly, the authors noted a statistically significant reduction in DLco and a non-significant
trend toward reduction in total lung capacity in those patients with esophageal
diameters >9 mm. This findings may suggest that DLco is a more sensitive marker of lung injury
related to silent aspiration as has been shown in other forms of lung injury.
In 2012, Patiwetwitoon et al. published results from another study
involving 71 patients with SSc and showed a significant correlation between the
extent of honeycombing on HRCT and esophageal diameter (17). The authors did not
report PFTs results.
Lock and colleagues revealed
that SSc patients with hypomotility or aperistalsis on esophageal manometry had
lower lung volumes and lower DLco values (43). In addition, Richardson
et al. found that increasing esophageal diameter
on HRCT in SSc patients is associated with more severe radiographic ILD, lower lung
volumes, and lower CO diffusion (8). Marie et al. (57)
demonstrated that more severe esophageal motor abnormalities in SSc patients
were not only associated with a greater prevalence of ILD on HRCT scan and
lower baseline DLco, but also
they were associated with a greater deterioration of CO diffusion after 2 years.
Supporting the hypothesis that microaspiration may mediate the relationship
between esophageal dysmotility and SSc-ILD, Savarino et al. (58) showed that
the presence of pulmonary fibrosis on HRCT was associated with a greater number
of proximal reflux episodes on
pH-impedance monitoring in patients with SSc (58).
Although our study does
not prove a causal relationship between esophageal diameter and SSc-ILD, our
results are consistent with the findings of previous studies suggesting that GER
and microaspiration may be involved in the development and/or progression of SSc-ILD.
Three potential limitations to our
study need to be mentioned. Firstly, the nature of
this study is cross-sectional and the evaluation of the risk factors for ILD progression is not possible. Moreover, invasive esophageal studies were not performed routinely in
our cohort, and more detailed descriptions of some baseline variables, such as
pack-years of tobacco exposure or duration of disease-modifying anti-rheumatic
drug therapy were not available. Secondly, the generalizability
of our results can be limited by the single University recruitment. Thirdly, we had
no control group or patients with other causes of esophageal dysfunction to
compare with SSc patients. Therefore, our results apply exclusively to patients
In conclusion, we demonstrated that patients with SSc-ILD
had more dilated esophagi on chest HRCT compared with patients with SSc and no
significant lung disease. This finding is consistent with the hypothesis
that esophageal dysfunction has a role in development of lung disease in this
group. Using chest HRCT measurements has several advantages in assessing
esophageal dysfunction over the conventional methods (non-invasive, widely used
in SSc patients). Therefore, the detection of esophageal dilation in the early
stage of ILD may help to start early treatment and prevent further progression
of the lung disease (9,11). The current study was unable to evaluate this
possibility. Future longitudinal
studies to determine whether a dilated esophagus is a risk factor for ILD
progression should be designed to include careful assessment of SSc subset,
quantitative changes on HRCT scan of the lungs (23) and objective reference criteria for the GERD