Management of respiratory tract exacerbations in people with cystic fibrosis: Focus on imaging

Abstract

Respiratory tract exacerbations play a crucial role in progressive lung damage of people with cystic fibrosis, representing a major determinant in the loss of functional lung tissue, quality of life and patient survival. Detection and monitoring of respiratory tract exacerbations are challenging for clinicians, since under- and over-treatment convey several risks for the patient. Although various diagnostic and monitoring tools are available, their implementation is hampered by the current definition of respiratory tract exacerbation, which lacks objective "cut-offs" for clinical and lung function parameters. In particular, the latter shows a large variability, making the current 10% change in spirometry outcomes an unreliable threshold to detect exacerbation. Moreover, spirometry cannot be reliably performed in preschool children and new emerging tools, such as the forced oscillation technique, are still complementary and need more validation. Therefore, lung imaging is a key in providing respiratory tract exacerbation-related structural and functional information. However, imaging encompasses several diagnostic options, each with different advantages and limitations; for instance, conventional chest radiography, the most used radiological technique, may lack sensitivity and specificity in respiratory tract exacerbations diagnosis. Other methods, including computed tomography, positron emission tomography and magnetic resonance imaging, are limited by either radiation safety issues or the need for anesthesia in uncooperative patients. Finally, lung ultrasound has been proposed as a safe bedside option but it is highly operator-dependent and there is no strong evidence of its possible use during respiratory tract exacerbation. This review summarizes the clinical challenges of respiratory tract exacerbations in patients with cystic fibrosis with a special focus on imaging. Firstly, the definition of respiratory tract exacerbation is examined, while diagnostic and monitoring tools are briefly described to set the scene. This is followed by advantages and disadvantages of each imaging technique, concluding with a diagnostic imaging algorithm for disease monitoring during respiratory tract exacerbation in the cystic fibrosis patient.

Keywords: chest radiography; computed tomography, magnetic resonance imaging; cystic fibrosis; imaging; inflammation; lung function; respiratory tract exacerbations.

Figure 1

Adapted from “Exhaled 8-isoprostane and prostaglandin E(2) in patients with stable and unstable cystic fibrosis”: 8-Isoprostane concentrations in exhaled breath condensate in healthy subjects (open squares) and patients with stable (filled squares) and unstable (filled triangles)cystic fibrosis. Horizontal bars represent median values (61).

Figure 2

Posterior/anterior chest radiographs in (A) mild and (B) severe cystic fibrosis lung disease. Note the progressive increase of bronchial pathology in the subject with severe disease (B, arrows). The more severe the disease, the more difficult the detection of new abnormalities, especially during respiratory tract exacerbation.

Figure 3

Posterior-Anterior (PA) chest radiograph in mild (A) and severe (B) cystic fibrosis lung disease during respiratory tract exacerbation. Note large consolidation in the right lung base in image A indicating respiratory tract exacerbation (thick arrow) and bilateral consolidations in the right upper lobe and left lung base (B, thin arrows).

Figure 4

End-inspiratory CT of a cystic fibrosis patient (A) without and (B) with respiratory tract exacerbation, lung window. Note bronchiectasis and mucus plugs, especially in the middle lobe and lingula (thin arrows). The only difference indicating RTE is an increase in central mucus plugs (thick arrow).

Figure 5

Axial CT of 5 months old patients with CF, thickness 0.7 mm, scanned in single source-mode with pitch 1.2 (A) and repeated in double source-mode with pitch 3.2 (B). Note that respiratory artifacts are absent using an higher pitch acquisition (B), providing a high image quality and facilitating the detection of atelectasis in the left lower lobe (arrows).

Figure 6

Axial proton density-weighted PROPELLER free-breathing scan (A,B) and diffusion-weighted imaging (DWI) (b = 800 mm/s²) acquisition (C,D), both performed with a 1.5 T MRI system (MAGNETOM avanto, siemens healthineers, enlargen, Germany), in a patient with CF during respiratory tract exacerbation at baseline (A,C) and after treatment (B,D). Note the reduction in mucus plugs and DWI signal in the right lower lobe between baseline and follow-up (thin arrows), as well as the reduced consolidation and DWI signal in the lingula (thick arrows).

Figure 7

Axial CT (A), lung window, and axial T2-weighted MR image (B) in a CF patient with tree in bud in the posterior segment of the right upper lobe (thin arrow). Note loss in definition of lung abnormalities in the MR image, where peripheral abnormalities may be not be visible in the MRI sequence (B, thick arrow).

Figure 8

Coronal reformatted CT (A) and coronal ultra-short TE (UTE) MR scan (B) in a cystic fibrosis patient during respiratory tract exacerbation. Note the high definition of lung abnormalities in both CT and MRI in the right lung (circles).

Figure 9

16 years old boy with cystic fibrosis during respiratory tract exacerbation. T2-weighted PROPELLER image (A), T1-weighted (B) pre and post-contrast (C) gradient-echo acquisitions, performed on 1.5 T MRI system (MAGNETOM Avanto, Siemens Healthineers, Enlargen, Germany). Note that in T2-weighted scan bronchial wall cannot be identified in the large bronchiectasis with mucus plugging in the right upper lobe (A, arrow). Gadolinium injection allows identification of bronchial wall thickening and to distinguish between bronchial wall and mucus plugs (C, arrow).

Figure 10

Ventilation maps taken before (A) and after (B) respiratory tract exacerbation treatment in a patient with CF, obtained by Fourier decomposition MRI. Note the ventilation defects in the upper lobes at baseline (thin arrows), which improved after treatment, especially in the right lung (thick arrow).

Figure 11

Workflow of the proposed imaging algorithm. CF, Cystic fibrosis; CR, Chest Radiography; CT, computed tomography; MRI, magnetic resonance imaging; RTE: respiratory tract exacerbation; # recent CT or MRI not available (<2 years); $, center with no MRI or no MRI experience; +, positive CR findings; −, negative CR findings.