Congenital Subglottic Stenosis
The reported incidence of congenital airway anomalies in infants who present with respiratory insufficiency ranges from 37 to 85% . Precise diagnosis of the congenital anomaly is often difficult, and requires a multi-modality approach involving the otolaryngologist, pulmonologist, gastroenterologist, and radiologist. Commonly occurring congenital anomalies of the upper respiratory tract include laryngomalacia, tracheomalacia, subglottic stenosis, glottic web, vocal cord paralysis, tracheal stenosis, laryngeal stenosis, laryngeal clefts, tracheoesophageal fistula, and subglottic hemangioma . Even with an accurate diagnosis, available treatments options are limited. About 10 to 14% of these children will require a long-term trache-otomy.
The option of surgical reconstruction is available for children with laryngeal stenosis, subglottic stenosis, tracheal stenosis, laryngeal clefts, or tracheoesophageal fistulas. However, these surgical interventions entail a modest success rate, significant morbidity, and a disproportionate allocation of health care resources. Furthermore, few institutions are equipped to manage the more severe cases, leading to a high mortality rate in children who do not have access to the appropriate resources. Of the morbidities associated with tracheotomy or upper respiratory tract reconstruction, speech delay, developmental delay, dysphonia and dysphagia are the most frequent and persistent . Therefore, despite the ability to survive through infancy, children with congenital upper respiratory tract anomalies attain only a marginal quality of life. For these reasons, it is essential to advance this area of pediatric disease and seek more efficacious diagnostic and treatment modalities.
The current state of the field is limited to gross anatomical descriptions of the normal embryology of the upper respiratory tract and commonly occurring congenital anomalies. To develop more efficacious diagnostic and treatment modalities, it is essential to develop an understanding of the pathophysiology of these lesions. This will first require a mechanistic understanding of normal upper respiratory tract embryology. Data from such endeavors will then help develop hypotheses regarding the pathophysiology of congenital upper respiratory tract anomalies, acquired respiratory tract lesions, and catalyze efforts to develop better diagnostic and treatment regimens.
Table 1. Commonly Encountered Congenital Airway Anomalies.
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Laryngomalacia |
Cartilaginous support structures of larynx lack integrity |
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Tracheomalacia |
Foreshortened tracheal rings; Tracheoesophogeal septum lacks integrity |
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Subglottic Stenosis |
Elliptical or small cricoid ring |
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Laryngeal Cleft |
Defect in posterior lamina of Cricoid ring |
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Complete Tracheal Rings |
Tracheal cartilage rings forms complete rings |
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The cartilaginous support structure represents a key sub-element of the upper airway, providing the integrity to keep the laryngeal tracheal lumen patent and provide attachments for associated muscles. The physiological importance of the cartilaginous support structure is emphasized by the fact that most clinically relevant congenital anomalies of the upper airway involve defects in the cartilaginous subcomponent (Table I). The laryngeal-tracheal skeleton is made up of several cartilaginous structures strung together in series and suspended from the skull base and mandible (Figure I). The thyroid cartilage is composed of two halves fused anteriorly at a sharp angle (90 degrees in males, and 120 degrees in females). The superior cornu attaches to the thyrohyoid ligament, while the inferior cornu articulates with the cricoid cartilage. The cricoid cartilage is the skeletal support of the subglottis, which is the portion of the larynx below the vocal folds. The subglottis is the only point in the airway with a completely rigid diameter. Anteriorly, the cricoid is about 1 cm high, with a smooth, curved surface. Posteriorly, it is 2 to 3 cm high, and the superior surface is flattened centrally to provide an area of articulation for the arytenoid cartilages. Two other small sesamoid cartilages, the corniculate and the cuneiform, are located superior to the arytenoid and support the aryepiglottic fold. Attached to the inferior aspect of the cricoid are the tracheal cartilage rings. Tracheal cartilage is in fact a C-shaped structure, with the incomplete part of the ring facing posteriorly. The two free edges of the tracheal cartilage ring are bridged by the muscular trachealis. The trachealis is one of several components that compose the tracheoesophogeal septum, the soft tissue separating the respiratory and digestive tracts. There are on average 17 tracheal cartilage rings in the human trachea interconnected by intervening fibroelastic tissue. C-shaped cartilaginous support structures, similar to that found in the trachea, continue to the level of the main stem bronchi.
Figure I
The current understanding of the embryology of the larynx and trachea is limited to descriptive anatomic studies in the mouse and post-mortem studies in human embryos . In the mouse, development is divided into the embryonic (E) period (first 16 days of gestation) and the subsequent fetal period (last 3 days of gestation). According to the Carnegie staging system (CS), the embryonic period has 23 stages. Laryngeal and tracheal development begins at stage 11 and can be divided into eight phases (Figure II). During phase I (CS 11, E9.5), the first sign of the respiratory system is seen as an epithelial thickening along the ventral aspect of the foregut, known as the respiratory primordium. The respiratory primordium is a rest of mesenchymal cells, which will give rise to the muscle and cartilaginous components of the upper airway and lung. During phase II (CS 12, E10) the respiratory diverticulum forms as an out-pouching of the foregut endoderm. The respiratory diverticulum expands into the respiratory primordium and is enveloped in mesenchymal cells. During the later aspect of this phase, broncho-pulmonary buds appear from the lateral aspect of the respiratory diverticulum, and will eventually form the lower respiratory tract. The site of origin of the respiratory diverticulum is called the primitive pharyngeal floor and will eventually develop into the glottic region of the adult larynx. In phase III (CS 13-14, E10.5-11) there is caudocranial elongation of the foregut and a concomitant dorsocaudal elongation of both the respiratory diverticulum and broncho-pulmonary buds. The carina, which represents the location of the bifurcation of the main stem bronchi, originates from the caudal aspect of the respiratory diverticulum. With the continued caudal descent of the broncho-pulmonary buds, the main stem bronchi and distal airways are formed and the carina appears as a separate and distinct region from the respiratory diverticulum. The trachea is formed from the increasing area between the respiratory diverticulum and the carina. Towards the end of this phase, the primitive laryngo-pharynx becomes compressed bilaterally by enlarging laryngeal mesodermal anlagen. The mesodermal anlagen, derived from the second, third, fourth and fifth branchial arches, will give rise to laryngeal cartilage and musculature. During phase IV (CS 15, E11.5-12) the bilateral compression of the laryngopharynx results in obliteration of the ventral aspect of the primitive laryngopharynx and the creation of the epithelial lamina. In phase V (CS 16, E12-12.5) the laryngeal mesodermal anlagen consolidates into two distinct masses, the hyoid anlage and the cricothyroid anlage complex. The cricothyroid anlage is composed of a U-shaped thyroid anlage superiorly and the cricoid anlage inferiorly. The cricoid anlage is composed of three parts, one ventromedian component and two dorsolateral components. Growth and fusion of these three components during the next phase is required to form the complete ring of the adult cricoid. During phases VI (CS 17-18, E13-14) and VII (CS 19-23, E15-16) the epithelial lamina begins to recanalize. The last portion of the primitive laryngopharynx to recanalize is at the glottic level. The final step, phase VIII (fetal day17-19), entails completion of the recanalization, and establishment of a complete connection between the supraglottis and infraglottis.
Figure II
Genetic Etiology of Congenital Airway Anomalies
Role of the Transcriptor Factor SOX9 in tracheal cartilage Development