Magnetic resonance imaging detects onset and association with lung disease severity of bronchial artery dilatation in cystic fibrosis

Patricia Leutz-Schmidt, Daiva-Elzbieta Optazaite, Olaf Sommerburg, Monika Eichinger, Sabine Wege, Eva Steinke, Simon Y. Graeber, Michael U. Puderbach, Jens-Peter Schenk, Abdulsattar Alrajab, Simon M.F. Triphan, Hans-Ulrich Kauczor, Mirjam Stahl, Marcus A. Mall, Mark O. Wielpütz
ERJ Open Research 2023 9: 00473-2022; DOI: 10.1183/23120541.00473-2022

Abstract

Background Bronchial artery dilatation (BAD) is associated with haemoptysis in advanced cystic fibrosis (CF) lung disease. Our aim was to evaluate BAD onset and its association with disease severity by magnetic resonance imaging (MRI).

Methods 188 CF patients (mean±sd age 13.8±10.6 years, range 1.1–55.2 years) underwent annual chest MRI (median three exams, range one to six exams), contributing a total of 485 MRI exams including perfusion MRI. Presence of BAD was evaluated by two radiologists in consensus. Disease severity was assessed using the validated MRI scoring system and spirometry (forced expiratory volume in 1 s (FEV1) % pred).

Results MRI demonstrated BAD in 71 (37.8%) CF patients consistently from the first available exam and a further 10 (5.3%) patients first developed BAD during surveillance. Mean MRI global score in patients with BAD was 24.5±8.3 compared with 11.8±7.0 in patients without BAD (p<0.001) and FEV1 % pred was lower in patients with BAD compared with patients without BAD (60.8% versus 82.0%; p<0.001). BAD was more prevalent in patients with chronic Pseudomonas aeruginosa infection versus in patients without infection (63.6% versus 28.0%; p<0.001). In the 10 patients who newly developed BAD, the MRI global score increased from 15.1±7.8 before to 22.0±5.4 at first detection of BAD (p<0.05). Youden indices for the presence of BAD were 0.57 for age (cut-off 11.2 years), 0.65 for FEV1 % pred (cut-off 74.2%) and 0.62 for MRI global score (cut-off 15.5) (p<0.001).

Conclusions MRI detects BAD in patients with CF without radiation exposure. Onset of BAD is associated with increased MRI scores, worse lung function and chronic P. aeruginosa infection, and may serve as a marker of disease severity.

Abstract

Bronchial artery dilatation in patients with cystic fibrosis can be detected with chest magnetic resonance imaging (MRI) and may occur as early as preschool age. It is strongly associated with lung disease severity on MRI and spirometry. https://bit.ly/3PvUDqL

Introduction

Lung disease determines >90% of morbidity and mortality in patients with cystic fibrosis (CF) [1–4]. Radiography and non-contrast-enhanced computed tomography (CT) are commonly used to assess lung morphology [5]. More recently, morpho-functional magnetic resonance imaging (MRI) has been introduced for radiation-free assessment of structural and functional abnormalities of the lungs in patients with CF [6–11]. A dedicated chest MRI scoring system has been validated to grade disease severity [12], and was shown to be sensitive to detect response to antibiotic therapy for pulmonary exacerbation including improvement of airway mucus plugging and of lung perfusion abnormalities in preschool- and school-age children with CF [6, 8]. More recently, studies investigating the effects of highly effective CF transmembrane conductance regulator (CFTR) modulator therapy with elexacaftor/tezacaftor/ivacaftor in adolescent and adult patients with at least one F508del mutation also demonstrated improvements in the MRI score, but failed to detect improvements in perfusion abnormalities [13, 14].

Bronchial artery dilatation (BAD) as an abnormality in pulmonary vascularisation in patients with CF is often first diagnosed at the time of pulmonary haemorrhage, experienced by 9.1% of all patients with CF during their lifetime [15, 16]. Massive haemoptysis with expectoration of >300 mL blood in 24 h is associated with high mortality, and bronchoscopy and angiographic embolisation of BAD are recommended treatments [17–19]. Although haemoptysis mainly occurs in adults with CF, it has also been reported in adolescents and children [15, 20, 21]. Often haemoptysis is observed during acute pulmonary exacerbations and can be treated conservatively. Previous studies used chest CT to detect BAD at the time of massive pulmonary haemorrhage in patients with CF [22]. Individual anatomy of bronchial arteries is highly variable, but usually two vessels per side arise from the proximal descending aorta at the level of the fifth and the sixth dorsal vertebra and serve as nutritive vessels for the airways and lung parenchyma [23]. Bronchial arteries in cases of BAD often show a morphologically distinct tortuous course in the mediastinum with an enlarged diameter of >2 mm [19, 24]. However, systematic imaging studies on the onset of BAD, and its association with structural and functional lung abnormalities detected by imaging, as well as lung function testing are entirely missing in CF. To date, contrast-enhanced CT angiography or invasive angiography required for its diagnosis are performed under emergency conditions only, but not for surveillance imaging [7, 25, 26]. Contrast-enhanced four-dimensional (4D) perfusion MRI comprises angiographic series in the pulmonary arterial and systemic arterial phase, and poses a unique opportunity to routinely screen for BAD in patients with CF undergoing chest MRI [6, 7, 11, 27]. Therefore, the present study was designed to study the onset of BAD by morpho-functional chest MRI and its association with disease severity. For this purpose, a cohort of 188 preschool to adult CF patients underwent a total of 485 standardised annual surveillance MRI studies, which were assessed by the validated chest MRI score, and spirometry.

Materials and methods

Subjects

This prospective observational study (ClinicalTrials.gov: NCT02270476) was approved by the institutional ethics committee of the University of Heidelberg (Heidelberg, Germany) and informed written consent was obtained from all patients or their parents or legal guardians. Chest MRI, spirometry and throat swabs were performed as part of annual surveillance visits. In total, 188 patients contributed 485 MRI studies (supplementary figure E1). Some patients were included in our previous reports but without analysing BAD [6, 8, 9, 28]. The diagnosis of CF was based on newborn screening and/or clinical symptoms, and confirmed by increased sweat chloride concentrations (≥60 mmol·L−1), CFTR mutation analysis and in pancreas sufficient patients with borderline sweat test results (chloride 30–60 mmol·L−1) by assessment of CFTR function in rectal biopsies (table 1 and supplementary table E1) [29, 30]. A chronic Pseudomonas aeruginosa infection was defined as persistence of P. aeruginosa for at least 6 consecutive months, or less when combined with increased levels (titre 1:1250) of two or more P. aeruginosa antibodies [8]. Spirometry (MasterScreen Body; Jaeger, Hoechberg, Germany) was performed from the age of 3 years according to established standards [31].

View this table:
TABLE 1

Characteristics of patients with cystic fibrosis (CF) without or with bronchial artery dilatation (BAD) at the time-point of magnetic resonance imaging (MRI)

Morpho-functional MRI

Standardised morpho-functional chest MRI was acquired with three clinical 1.5-T MR scanners (Magnetom Symphony, Avanto and Aera; Siemens Medical, Erlangen, Germany) as previously described and MRI protocols were kept essentially constant over the study period [6, 8, 9, 11–14, 27, 32]. Children ≤6 years of age were routinely sedated with oral or rectal chloral hydrate (100 mg·kg−1 body weight, maximum dose 2 g) and monitored during the MRI exam by MR-compatible pulse oximetry [6, 8, 28]. Specifically for detection of BAD, 4D perfusion imaging in coronal orientation with a resolution of 1.2×1.7×5.0 mm in patients aged ≤6 years to 2.2×1.6×5.0 mm in school-age children and adults was performed in a series of 20–30 whole-lung volumes at a temporal resolution of ∼1.5 s−1 during injection of 0.1 mmol·kg−1 body weight of a macrocyclic gadolinium-based contrast material (Dotarem; Guerbet, Villepinte, France or Gadovist; Bayer Schering, Leverkusen, Germany) at 2–5 mL·s−1 followed by a saline chaser (supplementary figure E2). An additional MR angiography at higher spatial resolution of 1.1×1.1×1.6 mm was acquired in adults [6, 33]. MR angiography was performed in two phases with an average of 16 s acquisition time each and a fixed delay of 10 s in between to allow for short respiration in between, in order to achieve pulmonary and systemic arterial enhancement. Further details are provided in the supplementary material.

MRI assessment

Structural and functional lung abnormalities were assessed using the dedicated MRI scoring system by a reader with >12 years of experience in chest MRI (M.O.W.) as previously described [6, 8, 9, 11, 12, 27, 28, 32]. In addition to the MRI scoring system, the presence of BAD was assessed by the same reader in consensus with a radiologist with >5 years of experience in chest MRI (P.L.S.). The time-point with maximal enhancement of the aorta was selected from the 4D perfusion MRI dataset and all visible vessels originating from the proximal aorta at the level of the carina were inspected (figure 1 and supplementary figure E2). Further details are provided in the supplementary material.

FIGURE 1
FIGURE 1

Representative examples of morpho-functional magnetic resonance imaging (MRI) detecting bronchial artery dilatation (BAD) in patients with cystic fibrosis (CF). Representative images of CF patients without and with BAD. Age and respective MRI global score are given above each set of images, with one column representing one patient. T1-weighted and T2-weighted morphological sequences were performed together with functional four-dimensional perfusion MRI. A 5-mm thick maximum intensity projection (MIP) is shown to enhance the delineation of BAD (white circles). Bronchiectasis/wall thickening is indicated by black arrows, mucus plugging by white arrows and consolidations by black arrowheads. Perfusion abnormalities are highlighted by white arrowheads.

Statistical analyses

Data were analysed using Prism (GraphPad, San Diego, CA, USA). Data are presented as mean with standard deviation unless otherwise specified. For the following analyses, only one MRI study per patient was taken into the analysis, which was either the most recent MRI study in patients without BAD or the first MRI study in which BAD was detected. The Wilcoxon rank-sum test was used for group comparisons. Receiver operating characteristic (ROC) curve analysis (area under the curve (AUC)) for the MRI score, patient age and FEV1 % pred versus presence of BAD was performed. A p-value <0.05 was considered statistically significant.

Results

MRI detects BAD in preschool- and school-age children and adults with CF

In total, 188 patients with CF contributed 485 MRI exams. The number of available MRI studies per patient ranged from one to six, with a median of three. In the entire study population, BAD was detected in 81 out of 188 (43%) CF patients, and from the MRI with first depiction of BAD, it was consistently present throughout all available follow-up exams (figure 1 and table 1). In the paediatric age group (≤18 years) BAD was detected in 36 out of 138 (26%) patients and in the adult age group BAD was detected in 45 out of 50 (90%) patients. On average, patients without BAD were younger with a mean±sd age of 8.3±6.3 years (range 1.1–29.3 years) compared with 21.0±10.8 years in patients with BAD (p<0.001). However, BAD was observed across a broad age range (2.2–55.2 years) in our study.

BAD is associated with higher MRI scores in patients with CF

MRI morphology, MRI perfusion and MRI global scores were increased in patients with BAD compared with patients without BAD (p<0.001) (figure 2 and table 1). Bronchiectasis/wall thickening was highly prevalent in both patient groups with or without BAD (p=0.16). However, mucus plugging and other findings such as abscess/sacculation, consolidation and pleural findings were significantly more prevalent in patients with versus without BAD (p<0.05–0.001) (figure 1 and table 1). Further, perfusion abnormalities were more frequent in patients with BAD compared with those without BAD (p<0.05). Accordingly, the subscores for bronchiectasis/wall thickening, mucus plugging, abscess/sacculation, consolidation and pleural findings were significantly increased when BAD was present (p<0.001).

FIGURE 2
FIGURE 2

Magnetic resonance imaging (MRI) scores in patients with cystic fibrosis without and with bronchial artery dilatation (BAD). a–c) Box-and-whisker plots of a) MRI morphology, b) MRI perfusion and c) MRI global scores. Boxes encompass the 25th percentile, median and 75th percentile, whiskers represent the 5th and 95th percentiles, and individual outliers are indicated by circles. p-values for group comparisons are shown for each panel. d) Scatter plot for MRI global score versus age. Dashed line indicates the cut-off of 15.5 points as determined by the receiver operating characteristic curve analysis.

FEV1 % pred was lower (p<0.001) and chronic P. aeruginosa infection was more common in patients with BAD compared with patients without BAD (p<0.001) (table 1).

Chest MRI score, age and spirometry predict presence of BAD in CF

To determine the sensitivity and specificity of markers of disease severity for the prediction of the presence of BAD on perfusion MRI, we performed a ROC analysis. In this analysis, the MRI global score performed well with a cut-off of 15.5 points, yielding 72.0% sensitivity and 90.1% specificity (Youden index 0.62, AUC 0.87, p<0.001) (figures 2 and 3). Age with a cut-off of 11.2 years yielded 71.0% sensitivity and 86.4% specificity (Youden index 0.57, AUC 0.86, p<0.001). FEV1 % pred with a cut-off of 74.2% yielded 88.4% sensitivity and 76.3% specificity (Youden index 0.65, AUC 0.87, p<0.001). In a multiple logistic regression model encompassing age, sex, pancreatic functional status, chronic P. aeruginosa infection status, FEV1 % pred and MRI global score, only age, FEV1 % pred and MRI global score yielded significant odds for BAD. The AUC of the model was 0.95 and thus improved compared with the ROC analysis of the individual predictors (figure 3 and table 2).

FIGURE 3
FIGURE 3

Receiver operating characteristic (ROC) curve analysis of the sensitivity of magnetic resonance imaging (MRI) scores, age and spirometry for the prediction of presence of bronchial artery dilatation (BAD) on MRI in patients with cystic fibrosis. a) ROC analysis for MRI morphology, MRI perfusion and MRI global scores. b) ROC analysis for age and forced expiratory volume in 1 s (FEV1) % pred. c) ROC analysis for the multivariate regression model from table 2 including age, sex, pancreatic functional status, chronic Pseudomonas aeruginosa infection status, FEV1 % pred and MRI global score. AUC: area under the curve.

View this table:
TABLE 2

Multiple logistic regression for the presence of bronchial artery dilatation on chest magnetic resonance imaging (MRI) in patients with cystic fibrosis

Development of BAD during longitudinal MRI surveillance

Of all 188 patients in our study, a subgroup of 10 (5%) patients developed BAD during surveillance imaging at a mean±sd age of 10.5±5.0 years (range 2.5–17.0 years) (figures 4 and 5, and table 3). The mean±sd time between the two consecutive scans before and with BAD was 1.3±0.6 years. In the 10 patients in whom BAD first occurred under surveillance imaging, MRI morphology, MRI perfusion as well as MRI global scores were significantly increased in the first exam with detection of BAD compared with the previous MRI (p<0.05). Moreover, FEV1 % pred was decreased at the time-point of the MRI with first detection of BAD compared with the time-point of the last exam without BAD (p<0.05) (table 3).

FIGURE 4
FIGURE 4

Representative example for the development of bronchial artery dilatation (BAD) in a 12-year-old male patient with cystic fibrosis detected by surveillance magnetic resonance imaging (MRI). Exams were acquired 2 years apart. BAD was not detected in the first MRI exam, but was present 2 years later. Age and respective MRI global score are given above each set of images. T1-weighted and T2-weighted morphological sequences were performed together with functional four-dimensional perfusion MRI. A 5-mm thick maximum intensity projection (MIP) is shown to enhance the delineation of BAD (white circle). Bronchiectasis/wall thickening is indicated by black arrows, mucus plugging by white arrows and consolidations by black arrowheads. Perfusion abnormalities are highlighted by white arrowheads. Note the deterioration of structural and perfusion abnormalities at the time of the second exam, in conjunction with the clear visibility of BAD with a typical course to the right lung.

FIGURE 5
FIGURE 5

Development of bronchial artery dilatation (BAD) is associated with increased magnetic resonance imaging (MRI) scores in patients with cystic fibrosis (CF). a–c) Before-and-after plots of a) MRI morphology, b) MRI perfusion and c) MRI global scores of 10 CF patients who developed BAD during routine surveillance MRI. p-values for intraindividual comparisons are shown for each panel.

View this table:
TABLE 3

Characteristics of school-age children with cystic fibrosis (CF) before and at first occurrence of bronchial artery dilatation (BAD) on magnetic resonance imaging (MRI)

Discussion

This study demonstrates that 4D perfusion MRI as a radiation-free imaging modality is sensitive to detect BAD in patients with CF and that its presence at MRI is associated with more severe lung disease as determined by the MRI score (figures 1–3 and table 1). BAD was already detected in some preschool children as young as 2 years of age and may be absent in adults as late as an age of 36 years. The MRI global score had a high discriminatory power for separating patients with from patients without BAD (figures 2 and 3). In general, age is associated with a higher disease severity on average, which has also previously been shown using imaging [8]. However, interindividual heterogeneity in disease severity is probably better reflected by the MRI score than age alone. We also demonstrate that patients with BAD have worse lung function as determined by spirometry and are more likely to have a chronic infection with P. aeruginosa (table 1). The multiple logistic regression model encompassing age, sex, pancreatic functional status, chronic P. aeruginosa infection status, FEV1 % pred and MRI global score achieved an excellent AUC for the prediction of BAD (figure 3). Furthermore, in a subset of 10 patients in our longitudinal MRI study we found that the first occurrence of BAD was accompanied by worsening of the MRI score compared with the last MRI without detection of BAD (figures 4 and 5, and table 3).

Some recent studies focused on the occurrence of haemoptysis in patients with CF, e.g. showing that 25% of patients with CF were under the age of 13 years when they had their first event of haemoptysis [34]. However, imaging data on the presence of BAD is missing for these studies. Until now it has not been fully understood which abnormalities of the lung parenchyma cause haemoptysis. Previous studies in adult non-CF patients found that the main associated pathology was bronchiectasis [35–37]. In view of our findings, it is conceivable that the previously described time-point of the first clinical occurrence of haemoptysis in CF at school age is within the same age range of the first occurrence of BAD as shown by our study. Taken together, these data indicate that BAD as a probably irreversible abnormality may occur early in life, depending on individual lung disease severity. It remains to be studied whether BAD plays a role during the first occurrence of haemoptysis. Since the reported recurrence rate of haemoptysis in CF is very high, ranging from 46% up to 100%, it may be important to monitor BAD in routine imaging and to potentially identify patients who are at risk for haemoptysis [21, 34, 38]. Future studies could demonstrate MRI's potential to detect the influence of embolisation of BAD on lung perfusion, patency and recurrence of BAD.

Recent studies investigating the effects of highly effective CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor in adolescent and adult patients with at least one F508del mutation demonstrated improvements in the MRI morphology score, but did not detect improvements in the MRI perfusion score despite a significant reduction in mucus plugging [13, 14]. These findings contrast with previous results from MRI studies in paediatric patients showing that antibiotic therapy for pulmonary exacerbation results in improved pulmonary perfusion [6, 8]. Our present data indicate that patients with BAD have more prevalent and more severe perfusion abnormalities (figure 2 and table 1). BAD is thought to be the result of a chronically increased inflow of blood into the pulmonary vascular bed from the systemic circulation, leading to an enlargement of the vessel diameter after an unknown period of time. Loss of integrity of the vessel wall may cause episodic or persistent bleeding into the bronchial lumen [17, 39]. Stimuli for recruiting systemic supply are chronic hypoxia, regional inflammation and recurrent or persistent infections [17, 39]. From recent MRI studies one could infer that locally increased structural lung abnormalities are in part associated with more severe perfusion abnormalities in this respective lobe [6]. Hypoxic pulmonary vasoconstriction is thought to account for reduced perfusion in areas of airway obstruction, but to date it has not been studied at which point of the pathophysiological process such perfusion changes become irreversible [6, 7]. Besides hypoxic pulmonary vasoconstriction, perfusion abnormalities are also related to chronic remodelling and loss of lung parenchyma with subsequent reduction of the vascular bed. Since this creates regional hypoxia paired with chronic inflammation, these processes may stimulate neovascularisation and thus increased blood inflow from the systemic circulation through the bronchial arteries. Thus, we speculate that the presence of BAD may indicate irreversibility of perfusion abnormalities due to tissue loss, as opposed to reversible perfusion abnormalities due to airway obstruction with hypoxic pulmonary vasoconstriction. It will be interesting to consider BAD as a novel biomarker associated with irreversibility of perfusion abnormalities under therapy in future studies.

This study has several limitations. First, we acknowledge that the perfusion MRI technique used in our study to detect BAD in preschool- and school-age children has limited resolution when compared with conventional invasive fluoroscopic or CT angiography. However, we sought to detect pathologically enlarged vessels, which usually have a diameter of ≥2 mm, which is clearly within the range of spatial resolution of 4D perfusion MRI [6, 27, 33]. This highly temporally resolved sequence is able to separate lung from systemic vessels due to the different time-course of enhancement after intravenous contrast material injection, which is not the case for CT angiography, but which facilitates detection of the systemic supply to the lungs in our present study [6–8]. Of note, MR angiography with even higher spatial resolution was additionally performed routinely in adult patients with CF. Invasive and CT angiography are techniques reserved for the emergency situation, and are not viable alternatives for disease monitoring due to radiation exposure and general invasiveness. CT imaging to assess CF lung disease is routinely performed at low dose and without contrast material application at most centres, which is not suitable to detect BAD [40]. Further, contrast-enhanced CT angiography of the chest which would be required to detect BAD is reserved for the emergency setting and is associated with a much higher radiation dose of ∼5 mSv in adults compared with low-dose CT which averages typically ∼1 mSv [41, 42]. Second, we were not able to determine the relationship between the presence of BAD and events of haemoptysis in our study, as this event has not been systematically documented in the database of our study cohort. Now that BAD can be detected with MRI, subsequent studies should assess the correlation between BAD and haemoptysis.

In summary, our results show that BAD in patients with CF can be detected with morpho-functional chest MRI protocols and that BAD can already occur as early as preschool age. Further, we found that BAD is strongly associated with increased lung disease severity, as determined by the MRI score and spirometry, and chronic P. aeruginosa infection. Early identification of BAD by radiation-free MRI may potentially be used in the future for the prevention of haemorrhagic events and may serve as a novel end-point indicating irreversible lung perfusion changes in CF.

Supplementary material

Supplementary Material

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Supplementary material 00473-2022.SUPPLEMENT

Acknowledgements

The authors thank all patients and their legal guardians for their participation in this study. Further, we acknowledge the significant contribution of magnetic resonance technicians, lung function specialists, study nurses and coordinators, as well as documentation assistants and data managers, for their key contributions in the collection of the study data.

Footnotes

  • Provenance: Submitted article, peer reviewed.

  • This study is registered at ClinicalTrials.gov with identifier number NCT02270476.

  • Author contributions: Conception and design: P. Leutz-Schmidt, D-E. Optazaite, O. Sommerburg, M. Eichinger, S. Wege, E. Steinke, S.Y. Graeber, M.U. Puderbach, J-P. Schenk, A. Alrajab, S.M.F. Triphan, H-U. Kauczor, M. Stahl, M.A. Mall and M.O. Wielpütz. Acquisition, analysis and interpretation of data: P. Leutz-Schmidt, M. Eichinger, S. Wege, E. Steinke, S.Y. Graeber, J-P. Schenk, A. Alrajab, H-U. Kauczor, M. Stahl, M.A. Mall and M.O. Wielpütz. Writing the manuscript or revising it critically for important intellectual content: P. Leutz-Schmidt, D-E. Optazaite, O. Sommerburg, M. Eichinger, S. Wege, E. Steinke, S.Y. Graeber, M.U. Puderbach, J-P. Schenk, A. Alrajab, S.M.F. Triphan, H-U. Kauczor, M. Stahl, M.A. Mall and M.O. Wielpütz.

  • Conflict of interest: P. Leutz-Schmidt has nothing to disclose. D-E. Optazaite has nothing to disclose. O. Sommerburg declares payments for lectures and presentations from Vertex Pharmaceuticals, in the 36 months prior to manuscript submission. M. Eichinger declares clinical reader honoraria paid to their institution by Vertex Pharmaceuticals and speaker fees from Vertex Pharmaceuticals, in the 36 months prior to manuscript submission. S. Wege has nothing to disclose. E. Steinke declares funding from the Junior Clinician Scientist Program of Berlin Institute of Health – Charité Berlin, starting in July 2022; and a travel grant from Mukoviszidose e.V. to attend the European Cystic Fibrosis Young Investigator Meeting, Paris, 2022. S.Y. Graeber declares grants paid to their institution from Mukoviszidose e.V., Vertex Pharmaceuticals, the German Federal Ministry for Education and Research (BMBF) and Deutsche Forschungsgemeinschaft; and personal fees for presentations and serving on advisory boards from Chiesi GmbH and Vertex Pharmaceuticals, all in the 36 months prior to manuscript submission. M.U. Puderbach has nothing to disclose. J-P. Schenk declares an unpaid role as head of the radiology panel and member of the steering committee of the SIOP-RTSG association. A. Alrajab has nothing to disclose. S.M.F. Triphan has nothing to disclose. H-U. Kauczor declares funding to their institution for the present manuscript from Siemens. M. Stahl declares grants paid to their institution by Vertex Pharmaceuticals; and personal payments for serving on an advisory board from Vertex Pharmaceuticals, all in the 36 months prior to manuscript submission; as well as unpaid roles as Chairwoman of the FGM, Treasurer of the GPP and Secretary of the Cystic Fibrosis Group of the ERS. M.A. Mall declares funding paid to their institution for the work in the present manuscript from the German Federal Ministry for Education and Research (BMBF; grant 82DZL009B1); grants to their institution from Vertex Pharmaceuticals (IIS-2018-107555) and the Deutsche Forschungsgemeinschaft (DFG; CRC 1449–431232613); personal fees for consultancy from Boehringer Ingelheim, Arrowhead Pharmaceuticals, Vertex Pharmaceuticals, Santhera, Sterna Biologicals, Enterprise Therapeutics, Kither Biotech and Antabio; lecture fees from Boehringer Ingelheim, Arrowhead Pharmaceuticals and Vertex Pharmaceuticals; travel reimbursement from Boehringer Ingelheim and Vertex Pharmaceuticals; personal fees for participation on advisory boards from Boehringer Ingelheim, Arrowhead Pharmaceuticals, Vertex Pharmaceuticals, Santhera, Enterprise Therapeutics, Antabio and Kither Biotech, all in the 36 months prior to manuscript submission; and an unpaid role as an elected member of the ECFS board. M.O. Wielpütz declares funding paid to their institution for the work in the present manuscript from the German Federal Ministry for Education and Research (BMBF); grants, lecture fees and consultancy fees (all paid to their institution) from Boehringer Ingelheim and Vertex Pharmaceuticals, all in the 36 months prior to manuscript submission; and that they are an ESTI Board Member (personal payments) and an IWPFI Board Member (unpaid).

  • Support statement: This study was supported by grants from the German Federal Ministry of Education and Research (BMBF) (82DZL004A1 and 82DZL009B1 to M.A. Mall), and the Christiane Herzog Stiftung and the Mukoviszidose e.V. (grant 15/01 to M. Stahl). E. Steinke, S.Y. Graeber and M. Stahl are participants of the Berlin Institute of Health (BIH) – Charité Clinician Scientist Program funded by the Charité – Universitätsmedizin Berlin and the BIH. Funders had no involvement in the collection, analysis and interpretation of data, in the writing of the report or in the decision to submit the article for publication. Funding information for this article has been deposited with the Crossref Funder Registry.

  • Received September 14, 2022.
  • Accepted December 6, 2022.
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References

  1. ↵
    1. Bell SC,
    2. Mall MA,
    3. Gutierrez H, et al.
    The future of cystic fibrosis care: a global perspective. Lancet Respir Med 2020; 8: 65–124. doi:10.1016/S2213-2600(19)30337-6
    OpenUrlCrossRefPubMed
    1. Mall M,
    2. Boucher R
    . Pathogenesis of pulmonary disease in cystic fibrosis. Prog Respir Res 2006; 34: 116–121. doi:10.1159/000088489
    OpenUrl
    1. Mall MA,
    2. Hartl D
    . CFTR: cystic fibrosis and beyond. Eur Respir J 2014; 44: 1042–1054. doi:10.1183/09031936.00228013
    OpenUrlAbstract/FREE Full Text
  4. ↵
    1. Mall MA,
    2. Mayer-Hamblett N,
    3. Rowe SM
    . Cystic fibrosis: emergence of highly effective targeted therapeutics and potential clinical implications. Am J Respir Crit Care Med 2020; 201: 1193–1208. doi:10.1164/rccm.201910-1943SO
    OpenUrlCrossRefPubMed
  5. ↵
    1. Ley-Zaporozhan J
    . Thoraxbildgebung bei zystischer Fibrose. [Thoracic imaging in cystic fibrosis.] Radiologe 2020; 60: 802–812. doi:10.1007/s00117-020-00735-w
    OpenUrl
  6. ↵
    1. Wielpütz MO,
    2. Puderbach M,
    3. Kopp-Schneider A, et al.
    Magnetic resonance imaging detects changes in structure and perfusion, and response to therapy in early cystic fibrosis lung disease. Am J Respir Crit Care Med 2014; 189: 956–965. doi:10.1164/rccm.201309-1659OC
    OpenUrlCrossRefPubMed
  7. ↵
    1. Wielpütz MO,
    2. Eichinger M,
    3. Biederer J, et al.
    Imaging of cystic fibrosis lung disease and clinical interpretation. Rofo 2016; 188: 834–845. doi:10.1055/s-0042-104936
    OpenUrl
  8. ↵
    1. Stahl M,
    2. Wielpütz MO,
    3. Graeber SY, et al.
    Comparison of lung clearance index and magnetic resonance imaging for assessment of lung disease in children with cystic fibrosis. Am J Respir Crit Care Med 2017; 195: 349–359. doi:10.1164/rccm.201604-0893OC
    OpenUrlPubMed
  9. ↵
    1. Wielpütz MO,
    2. Eichinger M,
    3. Wege S, et al.
    Midterm reproducibility of chest magnetic resonance imaging in adults with clinically stable cystic fibrosis and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2019; 200: 103–107. doi:10.1164/rccm.201812-2356LE
    OpenUrl
    1. Woods JC,
    2. Wild JM,
    3. Wielpütz MO, et al.
    Current state of the art MRI for the longitudinal assessment of cystic fibrosis. J Magn Reson Imaging 2020; 52: 1306–1320. doi:10.1002/jmri.27030
    OpenUrl
  11. ↵
    1. Stahl M,
    2. Steinke E,
    3. Graeber SY, et al.
    Magnetic resonance imaging detects progression of lung disease and impact of newborn screening in preschool children with cystic fibrosis. Am J Respir Crit Care Med 2021; 204: 943–953. doi:10.1164/rccm.202102-0278OC
    OpenUrl
  12. ↵
    1. Eichinger M,
    2. Optazaite DE,
    3. Kopp-Schneider A, et al.
    Morphologic and functional scoring of cystic fibrosis lung disease using MRI. Eur J Radiol 2012; 81: 1321–1329. doi:10.1016/j.ejrad.2011.02.045
    OpenUrlCrossRefPubMed
  13. ↵
    1. Wucherpfennig L,
    2. Triphan SMF,
    3. Wege S, et al.
    Magnetic resonance imaging detects improvements of pulmonary and paranasal sinus abnormalities in response to elexacaftor/tezacaftor/ivacaftor therapy in adults with cystic fibrosis. J Cyst Fibros 2022; 21: 1053–1060. doi:10.1016/j.jcf.2022.03.011
    OpenUrl
  14. ↵
    1. Graeber SY,
    2. Renz DM,
    3. Stahl M, et al.
    Effects of elexacaftor/tezacaftor/ivacaftor therapy on lung clearance index and magnetic resonance imaging in patients with cystic fibrosis and one or two F508del alleles. Am J Respir Crit Care Med 2022; 205: 540–549. doi:10.1164/rccm.202110-2249OC
    OpenUrl
  15. ↵
    1. Flume PA,
    2. Yankaskas JR,
    3. Ebeling M, et al.
    Massive hemoptysis in cystic fibrosis. Chest 2005; 128: 729–738. doi:10.1378/chest.128.2.729
    OpenUrlCrossRefPubMed
  16. ↵
    1. Flume PA,
    2. Mogayzel PJ Jr.,
    3. Robinson KA, et al.
    Cystic fibrosis pulmonary guidelines: pulmonary complications: hemoptysis and pneumothorax. Am J Respir Crit Care Med 2010; 182: 298–306. doi:10.1164/rccm.201002-0157OC
    OpenUrlCrossRefPubMed
  17. ↵
    1. Brinson GM,
    2. Noone PG,
    3. Mauro MA, et al.
    Bronchial artery embolization for the treatment of hemoptysis in patients with cystic fibrosis. Am J Respir Crit Care Med 1998; 157: 1951–1958. doi:10.1164/ajrccm.157.6.9708067
    OpenUrlPubMed
    1. Hayes D Jr.,
    2. Winkler MA,
    3. Kirkby S, et al.
    Preprocedural planning with prospectively triggered multidetector row CT angiography prior to bronchial artery embolization in cystic fibrosis patients with massive hemoptysis. Lung 2012; 190: 221–225. doi:10.1007/s00408-011-9343-y
    OpenUrl
  19. ↵
    1. Monroe EJ,
    2. Pierce DB,
    3. Ingraham CR, et al.
    An interventionalist's guide to hemoptysis in cystic fibrosis. Radiographics 2018; 38: 624–641. doi:10.1148/rg.2018170122
    OpenUrlPubMed
  20. ↵
    1. Stern RC,
    2. Wood RE,
    3. Boat TF, et al.
    Treatment and prognosis of massive hemoptysis in cystic fibrosis. Am Rev Respir Dis 1978; 117: 825–828. doi:10.1164/arrd.1978.117.5.825
    OpenUrlPubMed
  21. ↵
    1. Barben JU,
    2. Ditchfield M,
    3. Carlin JB, et al.
    Major haemoptysis in children with cystic fibrosis: a 20-year retrospective study. J Cyst Fibros 2003; 2: 105–111. doi:10.1016/S1569-1993(03)00066-3
    OpenUrlCrossRefPubMed
  22. ↵
    1. Remy-Jardin M,
    2. Bouaziz N,
    3. Dumont P, et al.
    Bronchial and nonbronchial systemic arteries at multi-detector row CT angiography: comparison with conventional angiography. Radiology 2004; 233: 741–749. doi:10.1148/radiol.2333040031
    OpenUrlCrossRefPubMed
  23. ↵
    1. Cauldwell EW,
    2. Siekert RG
    . The bronchial arteries; an anatomic study of 150 human cadavers. Surg Gynecol Obstet 1948; 86: 395–412.
    OpenUrlPubMed
  24. ↵
    1. Furuse M,
    2. Saito K,
    3. Kunieda E, et al.
    Bronchial arteries: CT demonstration with arteriographic correlation. Radiology 1987; 162: 393–398. doi:10.1148/radiology.162.2.3797652
    OpenUrlCrossRefPubMed
  25. ↵
    1. Sly PD,
    2. Gangell CL,
    3. Chen L, et al.
    Risk factors for bronchiectasis in children with cystic fibrosis. N Engl J Med 2013; 368: 1963–1970. doi:10.1056/NEJMoa1301725
    OpenUrlCrossRefPubMed
  26. ↵
    1. Kuo W,
    2. Ciet P,
    3. Tiddens HA, et al.
    Monitoring cystic fibrosis lung disease by computed tomography. Radiation risk in perspective. Am J Respir Crit Care Med 2014; 189: 1328–1336. doi:10.1164/rccm.201311-2099CI
    OpenUrlCrossRefPubMed
  27. ↵
    1. Wielpütz MO,
    2. von Stackelberg O,
    3. Stahl M, et al.
    Multicentre standardisation of chest MRI as radiation-free outcome measure of lung disease in young children with cystic fibrosis. J Cyst Fibros 2018; 17: 518–527. doi:10.1016/j.jcf.2018.05.003
    OpenUrlPubMed
  28. ↵
    1. Stahl M,
    2. Wielpütz MO,
    3. Ricklefs I, et al.
    Preventive Inhalation of Hypertonic Saline in Infants with Cystic Fibrosis (PRESIS). A randomized, double-blind, controlled study. Am J Respir Crit Care Med 2019; 199: 1238–1248. doi:10.1164/rccm.201807-1203OC
    OpenUrlPubMed
  29. ↵
    1. Graeber SY,
    2. Vitzthum C,
    3. Pallenberg ST, et al.
    Effects of elexacaftor/tezacaftor/ivacaftor therapy on CFTR function in patients with cystic fibrosis and one or two F508del alleles. Am J Respir Crit Care Med 2022; 205: 540–549. doi:10.1164/rccm.202110-2249OC
    OpenUrl
  30. ↵
    1. Hirtz S,
    2. Gonska T,
    3. Seydewitz HH, et al.
    CFTR Cl– channel function in native human colon correlates with the genotype and phenotype in cystic fibrosis. Gastroenterology 2004; 127: 1085–1095. doi:10.1053/j.gastro.2004.07.006
    OpenUrlCrossRefPubMed
  31. ↵
    1. Miller MR,
    2. Hankinson J,
    3. Brusasco V, et al.
    Standardisation of spirometry. Eur Respir J 2005; 26: 319–338. doi:10.1183/09031936.05.00034805
    OpenUrlAbstract/FREE Full Text
  32. ↵
    1. Triphan SMF,
    2. Stahl M,
    3. Jobst BJ, et al.
    Echo time-dependence of observed lung T1 in patients with cystic fibrosis and correlation with clinical metrics. J Magn Reson Imaging 2020; 52: 1645–1654. doi:10.1002/jmri.27271
    OpenUrl
  33. ↵
    1. Wucherpfennig L,
    2. Triphan SM,
    3. Weinheimer O, et al.
    Reproducibility of pulmonary magnetic resonance angiography in adults with muco-obstructive pulmonary disease. Acta Radiol 2022; in press [https://doi.org/10.1177/02841851221111486]. doi:10.1177/02841851221111486
  34. ↵
    1. Efrati O,
    2. Harash O,
    3. Rivlin J, et al.
    Hemoptysis in Israeli CF patients – prevalence, treatment, and clinical characteristics. J Cyst Fibros 2008; 7: 301–306. doi:10.1016/j.jcf.2007.11.007
    OpenUrlCrossRefPubMed
  35. ↵
    1. Dabo H,
    2. Gomes R,
    3. Marinho A, et al.
    Bronchial artery embolisation in management of hemoptysis – a retrospective analysis in a tertiary university hospital. Rev Port Pneumol 2016; 22: 34–38. doi:10.1016/j.rppnen.2015.09.001
    OpenUrl
    1. Soares Pires F,
    2. Teixeira N,
    3. Coelho F, et al.
    Hemoptysis – etiology, evaluation and treatment in a university hospital. Rev Port Pneumol 2011; 17: 7–14. doi:10.1016/S0873-2159(11)70004-6
    OpenUrlCrossRefPubMed
  37. ↵
    1. Fruchter O,
    2. Schneer S,
    3. Rusanov V, et al.
    Bronchial artery embolization for massive hemoptysis: long-term follow-up. Asian Cardiovasc Thorac Ann 2015; 23: 55–60. doi:10.1177/0218492314544310
    OpenUrlCrossRefPubMed
  38. ↵
    1. Antonelli M,
    2. Midulla F,
    3. Tancredi G, et al.
    Bronchial artery embolization for the management of nonmassive hemoptysis in cystic fibrosis. Chest 2002; 121: 796–801. doi:10.1378/chest.121.3.796
    OpenUrl
  39. ↵
    1. McDonald DM
    . Angiogenesis and remodeling of airway vasculature in chronic inflammation. Am J Respir Crit Care Med 2001; 164: S39–S45. doi:10.1164/ajrccm.164.supplement_2.2106065
    OpenUrlCrossRefPubMed
  40. ↵
    1. Kuo W,
    2. Kemner-van de Corput MP,
    3. Perez-Rovira A, et al.
    Multicentre chest computed tomography standardisation in children and adolescents with cystic fibrosis: the way forward. Eur Respir J 2016; 47: 1706–1717. doi:10.1183/13993003.01601-2015
    OpenUrlAbstract/FREE Full Text
  41. ↵
    1. Pontana F,
    2. Moureau D,
    3. Schmidt B, et al.
    CT pulmonary angiogram with 60% dose reduction: influence of iterative reconstructions on image quality. Diagn Interv Imaging 2015; 96: 487–493. doi:10.1016/j.diii.2014.08.006
    OpenUrl
  42. ↵
    1. Metaxas VI,
    2. Dimitroukas CP,
    3. Efthymiou FO, et al.
    Patient dose in CT angiography examinations: an institutional survey. Radiat Phys Chem 2022; 195: 110083. doi:10.1016/j.radphyschem.2022.110083
    OpenUrl
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Magnetic resonance imaging detects onset and association with lung disease severity of bronchial artery dilatation in cystic fibrosis
Patricia Leutz-Schmidt, Daiva-Elzbieta Optazaite, Olaf Sommerburg, Monika Eichinger, Sabine Wege, Eva Steinke, Simon Y. Graeber, Michael U. Puderbach, Jens-Peter Schenk, Abdulsattar Alrajab, Simon M.F. Triphan, Hans-Ulrich Kauczor, Mirjam Stahl, Marcus A. Mall, Mark O. Wielpütz
ERJ Open Research Mar 2023, 9 (2) 00473-2022; DOI: 10.1183/23120541.00473-2022
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