Pediatric Pulmonology, Supplement 2310-12 (2001)

Tracheal Dyskinesia Associated With Midline Abnormality:

Embryological Hypotheses and Therapeutic Implications

A. Corre, F. Chaudre, G. Roger, F. Denoyelle, and E.N. Garabedian

ABSTRACT

Abnormalities of tracheal rigidity, which may lead to the collapse of the airway during expiration and con- sequent complications, characterize two groups of disorders: tracheomalacia (weakness of the anterior cartilaginous arc of the trachea) and tracheal dyskinesia (dysfunction of the posterior membranous trachea).

Tracheal dyskinesia can either be isolated or associated with a more complex syndrome of malformations: esophageal atresia, tracheoesophageal fistula and laryn- gotracheal cleft. Although our knowledge of the embryo- logical development of the tracheoesophageal axis remains limited, the existence of these associations suggests that tracheal dyskinesia is of congenital origin.

The presentation of three clinical cases demonstrates that the coexistence of a midline malformation and of tracheal dyskinesia complicates the therapeutic manage- ment of the first malformation. In particular, the posto- perative follow-up is often more difficult, and a long-term tracheostomy is often required (sometimes for several years). However, it must be pointed out that tracheal dyskinesia, even in the associated forms, has a good long- term prognosis, since spontaneous resolution as the child grows up is the rule.

INTRODUCTION

Abnormalities of tracheal rigidity, which may lead to the collapse of the airway during expiration and its consequences (stridor or wheezing, cough, dyspnea and repeated bronchopulmonary infections) are frequently classified under the term of tracheomalacia. However, it is important, as we have already described,’ to differ- entiate “true” tracheomalacia, that is weakness of the anterior cartilaginous arc of the trachea, from tracheal dyskinesia, where the collapse is due to an elevation of the posterior wall into the tracheal lumen. The distinction between these two entities, which may nevertheless be associated, is not purely academic. In fact, they differ with respect to their origin, their possible association with more complex malformative syndromes and their ther- apeutic management. 0 2001 Wiley-Liss, Inc.

We present three cases of tracheal dyskinesia asso- ciated with an anomaly in the development of the laryngotracheoesophageal axis, which demonstrate the problems encountered in the management of this com- bination of malformations. We will also summarize our current knowledge of the embryological development of these structures, which suggests that the association of these anomalies is not a chance occurrence and that a tracheal dyskinesia may be congenital in origin.

CLINICAL CASES

S. H., born 22/08/95 A type I1 laryngeal cleft (stretching to the second

tracheal ring) was discovered in September 1996, at the age of 13 months, following repeated episodes of bronchitis associated with aspiration when feeding. The patient underwent three operations (September 96, December 96, May 97). Severe postoperative tracheal dyskinesia required spontaneous ventilation with positive pressure (BIPAP) from February 97 to May 97 and then tracheostomy during the third surgical intervention. Progressive improvement in the tracheal dyskinesia enabled the tracheostomy to be closed in January 98 (total time with a tracheostomy: 8 months).

A. N. , born 3/02/96 The patient presented with neonatal respiratory distress

requiring intubation. The VACTERL syndrome (a mid- line anomaly) was discovered with a persistent ductus arteriosus, a single umbilical artery, anal malformation and a type I11 esophageal atresia with a voluminous tracheoesophageal fistula. Surgical intervention was performed on the esophagus on the second day of life. Subglottic stenosis probably of a mixed origin (con- genital and acquired) was found and required three interventions. Persistence of a severe tracheal dyskinesia

From the Department of ENT and Head and Neck Surgery, Armand Trousseau Children’s Hospital, Pans, France.

Address correspondence and reprint requests to Dr. E. N. GarabCdian, Department of ENT and Head and Neck Surgery, Armand Trousseau Children’s Hospital, 26, avenue du Dr. Arnold Netter, 75012 Pans, France.

Tracheal Dyskinesia 11

laryngeal folds (paired with respect to the midline) and an inferior tracheoesophageal fold. While the superior folds will descend, the inferior fold will ascend, and so it is the diminution in the tracheoesophageal space within the primitive foregut which will separate the trachea from the esophagus (and not a process of compartmentaliza- tion). This theory can explain laryngotracheal cleft (re- maining of tracheoesophageal space), esophageal atresia, but fails to explain tracheoesophageal fistula (authors propose a theory of vascular problems and cellular death).

More recently, Merei6.’ has used an animal (Adriamy- cin-treated, timed-pregnant rats) to induce esophageal or tracheal atresia to arrive at a more likely explanation: in the case of esophageal atresia, there is no division of the foregut, which forms the trachea in its upper section, whereas in the lower section, it forms lung buds and the distal esophagus which communicate by a tracheoeso- phageal or a bronchoesophageal fistula. The proximal esophagus appears as a dorsal outpouching of the foregut. Although epithelial differentiation of the trachea does occur (a posterior membrane with cartilage anteriorly), anomalies may be seen because this is direct differentia- tion of the primitive foregut and not the primitive trachea. In particular, the trachea is not supported posteriorly by the esophagus, and this may explain the weakness of the posterior membrane and the subsequent development of tracheal dyskinesia.

There are few histological studies of the musculature of the membranous trachea. Out of 500 tracheas from babies and children who had died of a variety of causes, Wailoo8 found two types of muscular fibres. The first was consistently present and consisted of transverse fibres stretching from the edge of one cartilaginous ring to another, without any intertwining and consequently providing little support to the membranous trachea. The second type of fibres, which was not consistently found, was situated behind the former fibres. This second type of fibre was particularly rare in premature babies as compared to older children. In addition, these fibres were more frequently found in the lower third of the trachea as compared to the upper two thirds. Finally, these fibres were often abnormally located (situated in front of the transverse fibres) in cases of tracheoesophageal fistula. This implies that these fibres are intertwined with the muscular fibres of the esophageal wall and, further- more, that they are probably involved in the rigidity of the membranous trachea. Indeed, the absence of these fibres could lead to tracheal dyskinesia, which is more frequent in premature babies, in the lower third of the trachea in cases where the entire trachea is not involved.’ Unfor- tunately, there have been no histological studies to date of the membranous trachea in children with tracheal dyskinesia. This is probably due to the usually good prognosis of isolated tracheal dyskinesia when adequate treatment is given.

necessitated a tracheostomy in September 96. Progressive improvement in the dyskinesia allowed decanulation in March 99 (total time with a tracheostomy: 30 months).

L.L., born 26/12/96 Intubation at one month of life was necessary due to

progressive respiratory deterioration. A type I1 laryngeal cleft was discovered with an incomplete posterior wall cleft stretching down to the carina. Surgical intervention was undertaken in April 97. An attempted extubation was unsuccessful due to severe tracheal dyskinesia and a tracheostomy was performed at the end of April 97. Progressive improvement in the dyskinesia allowed for decanulation in October 99 (total time with a tracheo- stomy: 30 months).

DISCUSSION

As shown in these clinical cases, the existence of tracheal dyskinesia makes the therapeutic management of associated tracheoesophageal malformations much more difficult. These malformations (essentially laryn- geal or laryngotracheal clefts and esophageal atresia with or without tracheoesophageal fistula) fall within what is usually described as “midline syndrome”. Tracheal dyskinesia can nevertheless be isolated and as such is often seen in prematurity and/or immaturity of the brain stem.’ The etiology of these isolated forms is difficult to address, but an association with a midline malformation suggests a congenital origin of the

However, the embryological development of the tra- cheoesophageal axis is not well described. The esophagus and the trachea arise from the same structure: the primitive foregut. The development of the trachea begins as a ventral outgrowth of the foregut on the 22”d day of embryological life. This then grows in a cranio-caudal direction, and subsequently divides into two lung buds between the 26” and 2fIth day of embryological life.4 It is generally acknowledged that the tracheoesophageal septum plays a determining role in the division of the foregut into the primitive trachea and esophagus. The classical theories (proposed by His in 1887 and reported by Kluth’) describe two lateral ridges, arising from the internal part of the lateral walls of the foregut, which point towards one another and join in the midline to form the tracheoesophageal septum. Although this theory is appealing, it cannot provide an explanation for certain anomalies such as laryngotracheal cleft (as the larynx is of branchial origin) or bronchoesophageal fistula. More- over, Kluth’ demonstrated that in chicken embryos these lateral ridges were not found during embryological development. Furthermore, he found that the splitting of the foregut into the trachea and the esophagus occurred by the development of folds in the foregut wall, which then approach each another, without actually fusing together. In the sagittal direction, he found two superior

12 Corre et at.

The therapeutic management, which is already difficult in cases of isolated tracheal dyskinesia, is even harder in dyskinesia associated with a midline abnormality. Indeed, treatment of the associated malformation is made even more difficult, since it is not rare that after surgical correction a pre-existing tracheal dyskinesia appears or deteriorates. Therefore, the dyskinesia puts an additional strain on the respiratory function and thereby very often prevents extubation and spontaneous ventilation (as was the case in our clinical examples). Because the natural evolution of dyskinesia is one of spontaneous improve- ment with the child's growth and given the fragility of these small patients who have already been operated on, it seems unreasonable to propose a further surgical inter- vention to correct the dyskinesia, as has been proposed by some authors: posterior tracheal graft," insertion of a tracheal stent or aortopexy.'* Also, in our opinion, the use of an endotracheal stent inserted endoscopically is contra-indicated due to the risk of laceration of the surgical sutures of the previous malformation repair.

Therefore, we advocate two alternative forms of management while waiting for a natural resolution:

spontaneous ventilation with positive pressure at the end of inspiration and expiration (BIPAP). This probably ought not to be used in the immediate posto- perative period because of the risk of loosening of surgical sutures. We have experience with this treat- ment in cases of isolated dyskinesia and have seen excellent results. One patient in our series who had tracheal dyskinesia associated with a laryngotracheal cleft was given BIPAP. However, three months after starting this treatment, there was another relapse of the cleft although no formal link with the BIPAP therapy could be established; tracheostomy is our preferred treatment option in these cases despite the known morbidity and mortality of this technique in children.

It is important to maximize preventive medical treat- ment: prohibiting mixing with other infants, chest physio- therapy, treatment of gastro-esophageal reflux which is frequently present, prophylactic alternating courses of antibiotics and influenza vaccination. Endoscopic follow- up is essential at least once every three months in order to

detect relapse of the repaired malformation and, in particular, to assess the best timing for decanulation.

CONCLUSION

Tracheal dyslunesia, defined as expiratory collapse of the posterior membranous trachea, is a distinct entity from tracheomalacia. It probably arises as a congenital malformation when it is associated with a midline laryn- gotracheoesophageal abnormality. When isolated, tra- cheal dyskinesia is almost certainly an equivalent but minor malformation. Therefore, the work up in cases of isolated tracheal dyskinesia should be the same with respect to the detection of other malformations. Although the management of isolated dyskinesia is difficult, it is even more complicated when there is an associated midline malformation. In our experience, a tracheostomy, which may need to be of long duration, is the best option combined with preventive medical measures.

REFERENCES

I .

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

Loundon N, Brugel L, Roger G, Denoyelle F, Coiffier T, Garabedian EN. Current approach of primary tracheal dyskinesia. Pediatr Pulmunol 1999; 18(suppl):67-70. Mair EA, Parsons DS. Pediatric tracheobronchomalacia and major airway collapse. Ann Otol Rhino1 Laryngol 1992; 101:3OO-309. Mitchell DB, Koltai P, Matthew D, Bailey CM, Evans JNG. Severe tracheobronchomalacia associated with laryngeal cleft. Int J Pediatr Otorhinolaryngol 1989;18:181-185. Larsen WJ. Human Embryology. Churchill Livingstone Inc.; 1993. Kluth D, Steding G, Seidl W. The embryology of foregut malformations. J Pediatr Surg 1987;22:389-393. Merei JM, Farmer P, Hasthorpe S, Qi BQ, Beasley SW, Myers NA, Hutson JM. Timing and embryology of esophageal atresia and tracheo-esophageal fistula. Anat Rec 1997;249:240-248. Merei JM, Hasthorpe S, Farmer P, Hutson JM. Embryogenesis of tracheal atresia. Anat Rec 1998;252:271-275. Wailoo M, Emery JL. Structure of the membranous trachea in children. Acta Anat 1980;106:254-261. Couvreur J, Grimfeld A, Tournier G, Autier C, Le Moing G, Gaultier C, Gerbeaux J. La dyskintsie trachtale (trachtomalacie) chez l'enfant. Ann Ptdiatr 1980;27:561-570. Keller R, Herzog H. Surgical treatment of tracheal dyskinesia. Thorac Cardiovasc Surg 1983;31:352-354. De Lorimier AA, Harrison MR, Hardy K, Howell LJ, Adzick NS. Tracheobronchial obstructions in infants and children. Ann Surg 1990;212:277-289.