Computed tomography lung parenchymal descriptions in routine radiological reporting have diagnostic and prognostic utility in patients with idiopathic pulmonary arterial hypertension and pulmonary hypertension associated with lung disease

Routine radiological reports of the presence of emphysema or fibrosis have diagnostic and prognostic utility in patients diagnosed with IPAH

Differentiating PH-CLD from IPAH is an important part of the PH diagnostic algorithm and may be straightforward in the presence of severe lung function abnormalities or severe parenchymal lung disease, although in this study we still identified five patients (with mPAP of 55 mmHg) with severe emphysema who had been assigned a clinical diagnosis of IPAH. The presence of less severe degrees of lung disease provides more of a diagnostic challenge as has been highlighted by others [9, 11]. The 6th World Symposium on Pulmonary Hypertension (WSPH) task force suggested that patients with significant PH but only modest parenchymal abnormalities should be assigned a diagnosis of IPAH [5].

In the present study we found that radiological reports of emphysema or fibrosis in patients who had been clinically assigned a diagnosis of IPAH in keeping with the 6th WSPH recommendations was associated with significantly worse survival at Kaplan–Meier analysis. This supports the comments of Godinas et al. [11] who suggest that such patients represent a distinct group from those with IPAH being phenotypically closer to PH-CLD.

However, we also observed at Cox regression analysis that this prognostic importance of emphysema or fibrosis in patients diagnosed with IPAH was not independent of D_LCO. The prognostic importance of reduced D_LCO with or without coexisting parenchymal lung disease in patients assigned a diagnosis of IPAH has previously been reported [15–17]. We have previously demonstrated that response to PAH therapies in patients with IPAH-noLD and D_LCO <45% is lower than in patients with IPAH-noLD and D_LCO ≥45%, while on average patients with IPAH-LD exhibit a lack of response to PAH therapies in terms of exercise capacity and quality of life [15]. Therefore, the identification of emphysema or fibrosis on CT provides clinically relevant information in addition to that provided by D_LCO alone.

Routine radiological reports of the extent and nature of parenchymal lung disease have prognostic utility

In addition to the presence of parenchymal lung disease identified at routine reporting being associated with worse survival, we also observed that the extent and nature of lung disease described at routine reporting provided additional prognostic information. In patients originally assigned a diagnosis of IPAH, the extent of emphysema or fibrosis described qualitatively at reporting was strongly associated with prognosis. In patients with PH-CLD, the nature of parenchymal lung disease impacted on survival with the presence of fibrosis conveying a worse prognosis than emphysema, as previously described [18].

CGG in IPAH

CGG changes in the absence of emphysema or fibrosis were not uncommon, being reported in 23.3% of those IPAH patients who had no emphysema or fibrosis but were only reported in only 5.8% of patients with coexisting emphysema or fibrosis. The nature of CGG changes in patients diagnosed with IPAH is not clear. It is possible they represent pulmonary veno-occlusive disease (PVOD); however, we excluded patients with an additional radiological feature of PVOD (significant mediastinal lymphadenopathy or interlobular septal lines). Furthermore, there was no significant difference in D_LCO compared to IPAH-noLD patients without CGG changes. Nolan et al. [19] postulated that they represented cholesterol granulomas, while Horton et al. [20] presented a case report of a patient with fenfluramine-induced PAH with diffuse micronodules on CT who had an extensive diffuse plexogenic arteriopathy at lung biopsy [20]. In addition to IPAH, CGG changes have been commonly described in other forms of PAH including PAH associated with connective tissue disease and congenital heart disease [21]. In Eisenmenger syndrome and IPAH it has been postulated that this may be a feature of lung neovascularity [22, 23]. It is interesting to note that in our study there was no significant difference in survival compared with patients with IPAH-noLD at Kaplan–Meier analysis despite having significantly more severe pulmonary haemodynamics.

Limitations

This study has utilised clinical radiological reports involving semi-quantitative descriptions from the time of PH diagnosis rather than subsequent quantitative analysis. By using this approach, we have, however, been able to demonstrate that features described in routine “real-world” radiological reports have the ability to refine diagnostic and prognostic processes. It may well be that more in-depth quantitative analysis utilising artificial intelligence algorithms may provide superior diagnostic and prognostic information, and further studies are therefore warranted [24]. Selection or recall bias is minimised by using a “real-world” clinical cohort of consecutive patients diagnosed over 18 years. Misclassification bias is minimised by including all consecutive patients with lung disease and PH, not limiting to just an assigned diagnosis. An unavoidable limitation of a clinical cohort spanning 18 years is the variance in haemodynamic diagnostic criteria, treatment options and guidelines for patient management.

Conclusion

CT lung parenchymal descriptions in routine radiological reporting have diagnostic and prognostic utility in patients with IPAH and PH associated with chronic lung disease. Chest CT features should therefore be considered in patient assessment and risk stratification. Patients diagnosed with IPAH who have modest lung disease demonstrate unique clinical and survival characteristics and are likely to represent a distinct phenotype separate from IPAH. CGG changes are not uncommon in patients with IPAH and are associated with more severe pulmonary haemodynamics but non-inferior survival.