In the present study we analyzed 135 CTEPH patients and found that a decreased %FEV1.0 and %MMF were correlated with the degree of vascular obstruction and pulmonary hemodynamics. On analyzing the CTA obstruction score, pulmonary hemodynamics and PFT parameters one year after PEA, the %FEV1.0 was found to be improved with the improvement of CTA obstruction score and pulmonary hemodynamics. The improvement of the %FEV1.0 due to the improvement of vascular occlusion or stenosis is consistent with the findings of a previous study by Takei et al. describing balloon pulmonary angioplasty cases . Those findings suggest that the obstructive impairment in CTEPH patients might have an etiological correlation with the degree of vascular obstruction.
The present findings newly suggest that airway obstruction has an etiological correlation with vascular involvement in CTEPH. We excluded the CTEPH patients who had a smoking history in order to exclude obstructive impairment due to COPD as much as possible. In a previous case report, a CTEPH patient was misdiagnosed with bronchial asthma because of exertional dyspnea and a low FEV1.0 . A low FEV1.0 does not necessarily mean the presence of airway disease such as COPD and asthma in patients having exertional dyspnea. We should keep the possibilities of the pathophysiological condition with right heart burden including CTEPH in mind while carrying out a physical examination, chest X-ray, electro-cardiogram, etc.
Summarizing the previous studies, the pathological changes in CTEPH are characterized by thrombotic occlusion and remodeling of non-obstructed arteries induced by the flow diversion from obstructed arteries [21, 22]. In the area where pulmonary arteries are occluded, peripheral opacites caused by infarction are frequent findings on chest CT [23, 24]. Lung infarction could affect local airflow by collapsing the alveolar- bronchiole regions. On the other side, many papers described that the disparity in segmental vessel size reflecting the irregular distribution of emboli within the lungs was a characteristic finding of the CTEPH [23, 25, 26]. Local enlargement of the peripheral pulmonary arteries may lead to compression of bronchi nearby.
Another possible important factor of flow limitation underlying CTEPH is the concept of ‘‘inflammatory thrombosis’’. Various inflammatory substances are reportedly generated from blood clots and remodeled pulmonary arteries, including CRP , TNF-α , and MCP-1 . These cytokines are also reported to enhance the bronchial contraction [30–32]. In our results, significant correlation was observed between CTA obstruction score and the %FEV1.0 (Fig. 1). Inflammatory cytokines from blood clots in the subsegmental pulmonary arteries might lead to contraction of bronchioles nearby.
This is the first report to evaluate the respiratory impedance in patients with CTEPH, although the respiratory impedance parameters were poorly correlated with the spirometry parameters. The FOT is a method of measuring the lung mechanics that is better at the early detection of flow limitation than spirometry [33–35]. The correlation between the FOT and spirometry parameters has been previously reported. In COPD and asthma, R5 moderately correlates with the FEV1.0 and is thus used as an index of airway obstruction [36–38]. X5, Fres, and ALX are indicators of resistance of lung expansion or shrinkage and reflect abnormalities of the lung parenchyma . In the present study, the FOT parameters were poorly correlated with spirometry, in contrast to the previous studies mentioned above (Additional File 1). Because the respiratory impedance in CTEPH patients showed differing trends from those in COPD or asthma [37, 38], there might be an etiological difference between the obstructive impairment seen in CTEPH and that in COPD/asthma. Further investigations will help clarify the entire CTEPH etiology.
Several limitations associated with the present study warrant mention. First, the study design was a retrospective, single-center, observational study. Second, we were unable to clarify the detailed mechanism underlying the respiratory function changes because we were unable to perform pathological analyses. An additional multicenter investigation is therefore required.