Hypertrophied BA play a pivotal role in MH and are understood to be the culprit vessels [4, 6, 7]. However, attention has never been addressed to the actual size of BA in patients with CF and MH. To our knowledge, this study is the first to correlate BA diameter with the occurrence of MH in patients with CF. MH primarily occurs in advanced CF and often creates a life-threatening emergency situation. Although chronic inflammation and lung tissue destruction is present in basically all patients with end stage CF, only few patients develop MH . In addition, MH is not exclusively found in patients with advanced CF and higher age, but it also occurs in children and in patients with only minor pulmonary impairment rendering prediction of MH extremely challenging. This uncertainty leaves both patients and physicians in an unsatisfying situation when considering if and when to treat with BAE for hemoptysis [18, 19].
Despite major recent advances in treatment of CF with CFTR modulators , the number of patients with advanced CF and major destruction of lung tissue is high and will further increase over the next decades with rising life expectancy of patients with CF , most probably increasing the incidence of MH as well. Although lung transplant is a treatment option in recurrent and also MH, immediate life-saving treatment in case of MH will remain crucial [18, 19, 21]. As predictors of MH are scarce , their development is ever more important.
In our study BA diameters ≥ 3.5 mm were found in 76% of patients with MH (see Fig. 2A, B), whereas only in 29% of control group patients with end stage CF without hemoptysis (see Fig. 2C). However, these results might be biased as patients with bloody stained sputum and minor hemoptysis were excluded from control group in order to make differentiation of case and control group clearer. Another bias might have been created as median FEV1% pred. and also BMI of the control group are lower than in the case group. However, binary logistic regression analysis with MH as dependent variable and age, sex, FEV1 and BA diameter revealed BA diameter as the strongest independent risk factor (see Table 2). Influence of FEV1%pred. in BA diameter is minor. Control group patients had hypertrophied BA in 97%, but in the large majority (80%) only moderate hypertrophy was present. BA diameters ≥ 3.5 mm were found 2.6-fold, and BA diameters ≥ 4 mm were found 3.2-fold more often in patients with MH than in patients with end-stage CF but without history of hemoptysis. BA diameters were significantly larger in the case than in the control group creating an area under the curve of 0.719 in ROC calculation (see Fig. 1).
As BA are larger in the right lung in 90% of cases and BAE was carried out only or also on the right side in 84% of cases, we believe that measuring the largest BA in the mediastinum independent of lateralization is a feasible approach in daily routine reporting. Estimation of BA of the left lung should be considered with caution as only one of three patients showed larger BA diameters matching with MH only of the left lung. However, this number is too small for further interpretation and studies with larger numbers are necessary to create robust data for left lung BA diameter. In case of BAE special attention should be payed to patient’s perception of bleeding site as BA diameters of left lung and NBSA can be culprit vessels although they are not the largest BA/NBSA vessels. 85% of unilateral ssBACE cases were localized on the right side, which might be explained by the right lung generally being more affected by inflammatory changes than the left lung in CF . BA to be larger in the more affected lung further corroborates the hypothesis of BA hypertrophy as response to chronic inflammation [4, 6].
NBSA were present in both patient and control groups. NBSA can be a major source of bleeding in 41%–88% of patients with MH [23, 24]. These prevalence numbers are also concordant with our results of 36% of patients presenting NBSA, but 92% of detected NBSA considered culprit for MH and treated. Yoon et al. described a 100% detection rate of hypertrophied BA and NBSA in CTA compared to angiography . Both hypertrophied BA and NBSA could well be detected and measured in CTA with excellent correlation with measurements in DSA in the same patient. Diameters of NBSA however, did not exceed diameters of BA in the same patient and did not lead to upstaging neither in the patient nor in the control group. In addition, NBSA were found with comparable prevalence and slightly larger diameters in case group (3.2 mm (1.9 – 4.6 mm)) compared to control group 2.4 mm (1.7 – 3.9 mm). However, as 92% of detected NBSA were treated in case of MH, detection of hypertrophied NBSA is important and might serve as additional argument when considering BAE in hemoptysis.
BA diameter is not an underscore in any scoring system for CF. Routine CT scans for follow-up in patients with CF are usually carried out non-enhanced to appreciate lung parenchyma changes. Lack of contrast renders detection and measurement of BA and NBSA impossible (see Fig. 2D). In order to avoid secondary damage of ionizing radiation, morphologic lung tissue assessment is increasingly carried out as non-contrast enhanced magnetic resonance imaging (MRI) [8, 25]. BA could be detected in MRI angiography, but spacial resolution does not yet allow for BA/NBSA measurements . Therefore, to carry out CT scans as CTA in patients with CF and hemoptysis might help to evaluate BA diameter and presence of hypertrophied NBSA.
Estimating the risk of future MH should be based on several risk factors and including BA diameter measurement and detection of hypertrophied NBSA in patients with CF might add another important key in individual assessment. In addition, when considering BAE it is important to remember that patients with CF report stress or anxiety and fear of bleeding in public to negatively impact their quality of life . As BAE is effective and safe especially when carried out as coil embolization in treating MH, indication for BAE should also be considered in this context [6, 19, 21, 27]. In the literature several factors associated with MH have been published. MH seems to show higher prevalence with older age, FEV1% pred. < 70%, presence of diabetes and differing results for sputum colonization with Pseudomonas aerug. and S. aureus [2, 4, 6, 7, 23, 24]. Further prospective studies are necessary to validate if risk prediction of MH based on the criteria presence of NBSA and BA diameter > 3.5 mm is possible. Treatment of patients could then be safer and outcome better, as patients could be treated earlier, before occurrence of MH, in stable condition and, more importantly, not in an emergency setting.
Patients of control group did not receive DSA to verify BA diameters, but measurement of BA and NBSA was carried out in CTA in all patients of case and control group. In addition, comparison of DSA and CT scans was only carried out as proof of principle. BA diameter measurements in CTA and DSA to be comparable has been published in the literature  and showed excellent correlation in the case group. Patients with MH had CT scans with varying scanning protocols and devices but quality of CTA for detection of BA and NBSA was good to excellent in all cases. The small study group number is certainly a limitation as is the retrospective study design. However, MH is a rare complication treated in specialized centers with patients referred from all parts of Germany rendering larger cohort numbers and prospective studies difficult.