chest imaging in the study of primary ciliary … · chest imaging in the study of primary ciliary...

Neumol Pediatr 2019; 14 (2): 95 - 99

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Chest imaging in the study of primary ciliary dyskinesia in children

INTRODUCTION

Cilia cover the respiratory tract from the middle ear to the terminal bronchioles, playing a fundamental role in moving fluids, mucus and foreign materials inhaled from the distal to the proximal and then to the peripheral airway. They are important in the elimination of amniotic fluid from neonatal lungs and this mucociliary clearance is part of the defense mechanism of the respiratory tract (1). Any disorder that causes the cilia to be immobile, or become disturbed and disorients their movement, such as PCD, can be manifested with sinus and pulmonary symptoms. They can be shown as early as in neonates, in which the elimination of the amniotic fluid is delayed, which can cause transient tachypnea or neonatal pneumonia. Despite these early manifestations, diagnosis is delayed until childhood or even adulthood, with the average age of diagnosis being 4 years of age (2). Deterioration of mucociliary clearance of the lower respiratory tract leads to recurrent episodes of pneumonia or bronchitis, with frequent infections caused by Haemophilus influenzae, Staphylococcus aureus and Streptococcus pneumoniae, and Pseudomonas aeruginosa, in adults. Chronic lung infection and inflammation result in atelectasis and persistent bronchiectasis from very early ages, which usually affect the middle lobe and the lingula more frequently (1). The diagnostic algorithm of PCD is complex, and begins with high clinical suspicion, including electron microscopy, genetic tests and nasal nitric oxide testing. Findings in diagnostic

imaging are nonspecific and can be seen in other airway conditions, such as CF. In this review, we will describe PCD findings in simple radiology imaging and CT, with emphasis on some of the characteristics that differentiate it from CF, and we will review the role of CT in monitoring the structural changes in PCD. Finally, we will issue a brief comment on the role of pulmonary MR.

CHEST X RAY (RXTX)

Despite its low specificity and difficult interpretation, RxTx remains the most widely used imaging tool in the study of children with respiratory symptoms and signs, and is the most important tool in the study of respiratory distress in infants.RxTx is not sensitive to the early structural changes of the disease, however these are performed because they are widely available, cheap and with low amount of radiation(3). It is suggested to perform a RxTx at the time of diagnosis and during respiratory exacerbations; and in stable patients every 2 to 4 years to control the progression of the disease (4). RxTx findings include dextrocardia, which is present in 50% of cases. Lobar and segmental atelectasis and hyperinflation and pulmonary condensation may occur (Figure 1). To the extent that bacterial infections recur, chronic atelectasis and bronchiectasis may appear (2, 3).

MULTI SLICE CT SCAN OF THE CHEST (MSCT)

MSCT currently constitutes the imaging of choice for the study of the airway and the pulmonary parenchyma, with a high spatial and temporal resolution, the volumetric acquisition increases the potential of this technique, allowing by post processes to obtain high resolution 2D reconstructions

REVIEW ARTICLES

CHEST IMAGING IN THE STUDY OF PRIMARY CILIARY DYSKINESIA IN CHILDREN

ABSTRACT The diagnosis of primary ciliary dyskinesia (PCD) is complex and requires high clinical suspicion. The findings in the diagnostic images are nonspecific and can be seen in other conditions of the airway. In this review, we will describe the findings of PCD in chest radiography and computed tomography, with emphasis on some of the characteristics that differentiate it from cystic fibrosis and we will review the role of CT in the monitoring of changes of the PCD, since the CT findings correlate very well with the structural changes that occur in the course of PCD, especially bronchiectasis. However, using serial CTs should be decided on a case-by-case basis to avoid unnecessary radiation because they are pediatric patients.Key words: Primary ciliary dyskinesia, Computed Tomography, Bronchiectasis, Kartagener Syndrome.

Dr. Lizbet C. Pérez M. Pediatrician Radiologist. Hospital de Niños Luis Calvo Mackenna.Hospital Clínico de la Universidad de Chile. Clínica Alemana de Santiago. Clínica Indisa.

Correspondence:Servicio de Imaginología Hospital Clínico de la Universidad de ChileSantos Dumont 999 piso 1, sector D, Santiago - [email protected]

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in all the anatomical planes and 3D volumetric reconstructions. This provides images that are better understood by the rest of the non-radiological medical team, such as the VRT (Volume-rendering tomogram) and the minip (minimum intensity projection) reconstructions with which the entire anatomy of the tracheobronchial tree can be shown (5 ) (Figure 2). When evaluating diffuse airway diseases and pulmonary parenchyma MSCT can be performed without the use of intravenous contrast. A single acquisition is made in inspiration and if compromise of the small distal airway is suspected, cuts in expiration are added. Acting always under the ALARA principle (As Low As Reasonably Achievable), the radiation dose of the MSCT can be significantly reduced by modifying manufacturers' protocols, balancing the signal-to-noise ratio obtaining images that may be of lower "visual" quality but are "adequate for diagnostic purposes". Current bronchiectasis diagnosis includes CT, which helps describe the specific structural changes that occur in the lung. There are several scoring systems with CT for bronchiectasis related to CF that allow to correlate changes in CT

with the severity of the disease, changes over time, exacerbation and response to treatment. Some of these scoring systems have been used for PCD in the absence of a system of their own, this has allowed us to compare and differentiate these two entities, demonstrating a lower score and less seriousness of PCD in relation to CF (6). Other authors have found patterns of PCD, which are less frequent in CF, so they propose not to use CF scoring systems with PCD (7). CT in young children usually requires sedation or anesthesia, a factor to be taken into account when deciding to perform a CT scan. Likewise, it is suggested to perform a CT scan at least once when the child has reached 5-7 years of age, when sedation is no longer required and the images obtained can be of sufficient quality to detect bronchiectasis, using the lowest dose of radiation possible. Repeated CT imaging to monitor the progression of PCD has not been shown to improve the clinical course of the disease, this added to the fact that radiation doses are accumulative, makes this indication to be carefully evaluated case by case (4).

PCD FINDINGS IN MSCT

Bronchiectasis: defined by the Fleischner Society as "Irreversible localized or diffuse bronchial dilatation, usually resulting from chronic infection, proximal airway obstruction, or congenital bronchial anomaly." CT findings indicative of bronchiectasis are: bronchial dilatation in regard to the pulmonary artery ("seal ring sign") (Figure 3), Lack of normal bronchial tapering distal to bifurcation and visibility of peripheral airways within 1 cm of the costal pleura. It can be classified by its morphology into cylindrical, varicose or cystic (8). They are present in more than 50% of children affected by PCD, the most common locations are in the middle lobe, the lingula and the lower lobes, which contrasts with CF where the involvement of the upper lobes predominates (Figure 4). In these patients, diffuse involvement (5 lobes) and peripheral involvement are lower than in CF. The extent and severity of bronchiectasis increase with advancing age and worsening lung function (9).

Figure 1. RxTx AP and L of a 12-year-old boy diagnosed with PCD with situ solitus. It shows lobar atelectasis of the ML, with bronchial dilatations intra atelectasis, suggesting chronic atelectasis and bronchiectasis in the LRL, visible in the lateral projection. No significant alterations appear in the rest of the lungs.

Figure 2. CSI of a 12-year-old boy diagnosed with PCD. Volumetric acquisition with multiplanar reconstructions (MPR), 2D in conventional anatomical planes, axial, sagittal and coronal. It shows bronchiectasis and lobar atelectasis of the ML and the LRL, with indemnity of the upper lobes.

Figure 3. Axial section of a MDCT showing the seal ring sing (arrow) in the upper segment of the ILL, which is no more than an orthogonal section of the dilated bronchus (larger than the artery), with its accompanying pulmonary artery of normal caliber.

Neumol Pediatr 2019; 14 (2): 95 - 99



Mucous plugs: are produced by the replacement of air from the airway by mucous secretions. CT findings depend on whether the central or peripheral airway is compromised. Mucous plugs in CT manifest as fluid density material within the lumen of the bronchus, sometimes occupying the entire lumen or only the dependent portion of the lumen. It can compromise a lumen segment (Figure 5a) or branch out along the airways, giving the "finger-in-glove sign", this sign is more frequent in CF. Another sign that helps to recognize them is the "double artery sign", which corresponds to a non-dilated mucus- filled bronchus adjacent to a pulmonary artery, producing the appearance of a "double artery" on CT chest.(Figure 5b). Mucous plugs are more commonly described in adults than in children, but there are cohorts with children where they have been found in 85% of the cases (10). They are most

frequently located in the lower lobes and the peripheral lobes are more common than the central ones in PCD (11). The tree-in-bud pattern may represent mucosal impaction in the centrilobular bronchioles in these cases, and is more common and widespread in PCD than in CF (7) (Figure 6).

Peribronchial thickening: is a radiological descriptor that is used to describe an abnormal thickening of the walls of the bronchial tubes, which may be due to primary thickening of the wall, as in these cases, or by thickening of the interstitium around the wall. So in these specific cases we will be referring to the thickening of the bronchial wall. The thickening of the bronchial wall can be subjectively identified when the walls of the airways at the same level are thicker than the healthy airways (8) (Figure 6). The thickening of the bronchial wall is a universal finding of the MSCT of adult patients with PCD and of children. And like the rest of the findings, it is more frequent in the middle lobe, lingula and lower lobes (7, 11). Atelectasis: is the loss of volume of all or part of the lung. The mechanism in these cases is the reabsorption of air distal to the obstruction of the airway, especially in young children who have little development of the collateral airway. In CT imaging it manifests as a decrease in volume and increase in density in the affected part of the lung, which may be accompanied by abnormal displacement of the sulcus, bronchi, vessels, diaphragm, and mediastinum. Atelectasis distribution can be lobar, segmental or subsegmental. Linear atelectasis is a type of subsegmental atelectasis of linear shape that almost always contacts the pleura and its thickness can be from a few mm to more than 1 cm (8). Atelectasis related to PCD can be linear, lobar and segmental, these last two are seen more frequently (63%) in PCD than reported in CF and would be a structural change that differentiates them (7). The linear are less frequent (16%) in PCD

Figure 6. Segment of a high-resolution section at the level of the lingula, showing the dilatation and thickening of the wall of a subsegmental bronchus (gray arrow), we can see when comparing it with a normal subsegmental bronchus at this same level (black arrow). In this same section we can see (between the two white arrows) the mucosal impaction in the centrilobular bronchioles configuring the tree-in-bud pattern, more frequent in cases of PCD than in CF.

Figure 4. Sagittal reconstructions of MSCT of two 12-year-old patients, A, diagnosed with PCD and B, diagnosed with CF. The pulmonary structural compromise of B is much greater and more diffuse at the same age, with more bronchiectasis in all the pulmonary lobes and more subsegmental atelectasis, unlike A, where the characteristic is in regard to the upper lobes and atelectasis are lobar and segmental.

Figure 5a. Two oblique reconstructions of a segmental bronchus, with dense material occupying a segment of the lumen (arrow), which corresponds to a mucous plug with the finger-in-glove sign.Figure 5b. Axial section at the level of the lingula showing two parallel lines of similar density (arrow), one is an un dilated bronchus with mucus in the lumen and the other is its adjacent artery, which corresponds to the double artery sign.

Neumol Pediatr 2019; 14 (2): 95 - 99



and have not been reported in the upper lobes, in case of being present 75% occurs in the ML (6) (Figure 1 and 2). Air trapping: air trapping is a descriptor used in lung CT expiratory sections and corresponds to the areas of the pulmonary parenchyma of lower density and greater volume, in comparison with healthy lung parenchyma that increases its density and decreases in volume when taking out the air of the alveolar sacs at the end of expiration (8). Air trapping is described in almost all case series in literature, one of the most recent PCD reports describes it in 33 of 39 CTs in expiration, which represents a prevalence of 85% (7) (Figure 7).

Pulmonary parenchyma compromise: findings related to inflammatory / infectious changes of the lung parenchyma can be seen, which may be transient, within these findings are areas of peri bronchial consolidation, in relation to bronchiectasis, consolidations and areas of ground glass, central and peripherals. In general, these findings are less frequent in patients with PCD when compared with other diseases of the airway (9, 12). Jain found these changes in 62% of children with PCD (10). Other findings: Situs anomalies, Kennedy in 2007 found in 45 patients with PCD (29 adults and 16 children), situs solitus in 44%, situs inversus in 38% and heterotaxia in 18% (9). Classic Kartagener’s syndrome consists of the combination of bronchiectasis, sinusitis and situs inversus (13). Pectus excavatum has also been described, in 5 to 10% (9).

MAGNETIC RESONANCE IMAGING (MRI)

In the pediatric population, which is very susceptible to radiation, MRI has been introduced into clinical practice as an alternative to CT Imaging, and this has now reached the pathology of lung parenchyma. Regarding PCD, there are already several studies in the literature that classify CT findings with MR imaging as comparable to the extent and severity of the disease (14, 15).

In our environment, access to MRI remains limited, so we have not developed experience in lung MRI, however we believe it is a promising technique, especially in chronic diseases, where our children require periodic evaluations with CT imaging, which adds a dose of radiation.

CONCLUSIONS

PCD diagnosis requires high clinical suspicion and a set of diagnostic tests that do not include diagnostic images, however these are recommended in monitoring the progression of the disease. RxTx is the most basic imaging test with the lowest dose of radiation available for lung evaluation at the time of diagnosis, in the case of exacerbations and when there is suspicion of infection. CT findings show the structural changes that occur in the course of PCD, especially bronchiectasis, however there is currently no CT score specifically for this disease. Once diagnosed, a CT imaging is suggested at least once when the child cooperates, the decision to use repeated CTs should be decided on a case-by-case basis, and the lowest possible dose of radiation should always be used.

Conflict of interest:I declare no conflicts of interest with the review carried out.

Acknowledgments: To Dr. José Domingo Arce Valenzuela, my teacher, for providing the images of the Primary Ciliary Dyskinesia case here presented.

REFERENCES

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4. Shapiro AJ, Zariwala MA, Ferkol T, Davis SD, Sagel SD, Dell SD, et al. Genetic Disorders of Mucociliary Clearance Consortium. Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD foundation consensus recommendations based on state of the art review. Pediatr Pulmonol. 2016; 51(2):115-32.

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Figure 7. Inspiration and expiration axial MSCT at the subcarinal level. In expiration the air trapping corresponds to the areas of the lung of lower parenchyma density (more black), and the areas that increase in density (white) correspond to healthy lung parenchyma that has no compromise of the small distal airway and is able to remove the air from the alveolar sacs at the end of expiration, so that it decreases in volume (the vascular structures are seen closer together) and increases in density. The alternation of these areas of higher and lower density in expiration is known as "mosaic pattern" and is common to see in cases of PCD.


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C, et al. CF derived scoring systems do not fully describe the range of structural changes seen on CT scans in PCD. Pediatric Pulmonology 2019; 54: 471– 477.

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10. Jain K, Padley SPG, Goldstraw EJ, Kidd SJ, Hogg C, Biggart E, et al. Primary ciliary dyskinesia in the paediatric population: range and severity of radiological findings in a cohort of patients receiving tertiary care. Clinical Radiology 2007. 62, 986-993.

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13. Berdon W, Willi U. Situs inversus, bronchiectasis, and sinusitis and its relation to immotile cilia: history of the diseases and their discoverers – Manes Kartagener and Bjorn Afzelius. Pediatr Radiol 2004. 34: 38–42.

14. Montella S, Santamaria F, Salvatore M, Maglione M, Iacotucci P, De Santi MM, et al. Lung disease assessment in primary ciliary dyskinesia: a comparison between chest high-field magnetic resonance imaging and high-resolution computed tomography findings . Italian Journal of Pediatrics 2009, 35:24.

15. Maglione M, Montella S, Mollica C, Carnovale V, Iacotucci P, De Gregorio F, et al. Lung structure and function similarities between primary ciliary dyskinesia and mild cystic fibrosis: a pilot study. Italian Journal of Pediatrics 2017, 43:34.

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