Development of the airway in the fetus starts from as early as the fourth to fifth week postconception and the structures arise from the branchial arches. There is also an interaction of the blood vessels and the airways during early fetal development of the lungs, with the branching airways forming a template for vasculogenesis (1), hence patients with airway problems frequently have associated lung and cardiovascular abnormalities.

In addition, many airway problems are associated with congenital syndromes and anatomic variants that occur during this embryonic development. Many of these airway problems are now being diagnosed earlier and managed either surgically or in intensive care; hence, the need for neonatologists to be updated about the topic. It is also important for most doctors to be aware of the latest management, as these patients are now surviving into adolescence and early adulthood, thus needing transition of care from pediatricians to pulmonologists and introducing a whole new spectrum of conditions for respiratory physicians to deal with. The purpose of the review is to provide an update on the current investigations available to diagnose the condition, as well as to discuss the various treatment strategies presently available for management of the patient.

Airway problems can be broadly classified into congenital or acquired lesions and further divided into conditions causing obstruction of the airway and those due to an abnormal communication between the airway and esophagus. Congenital obstructive lesions can be from a simple intrinsic lesion in the airway (e.g., hemangiomata, cysts, and webs) or from abnormal development of the airway (e.g., congenital tracheal stenosis). Extrinsic compression can also occur from lesions external to the airway (e.g., vascular rings or slings, lymphangiomatous lesions, mediastinal tumors).

Congenital airway problems due to an abnormal communication (laryngotracheal clefts and tracheoesophageal fistulae) are frequently diagnosed at or soon after birth, because of the more obvious associated abnormalities (e.g., esophageal atresia, facial, and skeletal anomalies) or because of problems during feeding. However, the diagnosis of minor communications (e.g., H-type tracheoesophageal fistula or shorter laryngotracheal clefts) can be delayed, resulting in recurrent aspiration episodes before the diagnosis is eventually made.

Inflammation in the airway (either from infection or injury from endotracheal intubation or recurrent aspiration) can also lead to mucosal swelling causing breathing difficulties due to further reduction in the already small airway lumen. In the longer term, this can cause scarring and narrowing of the airway.

With the advancement of neonatal and pediatric intensive care practices, some of the airway problems we now see are acquired lesions (stenosis or malacia) following instrumentation of the airway and use of positive pressure ventilation or following newer therapies introduced for management of congenital problems. Major tracheobronchial abnormalities had been identified in preterm neonates with bronchopulmonary dysplasia even during the 1980s, with about half of them requiring surgical intervention (2–4). Higher averaged mean airway pressures during the first week after birth and lower gestational age were found to be clinical features associated with tracheomalacia (5). High pressure exerted on a developing airway or chronic inflammation, for example from intubation and mechanical ventilation, may cause weakness of the cartilaginous portion leading to tracheomalacia and acquired tracheomegaly. Recent trials where a balloon occlusion device is introduced into the fetal trachea, in an attempt to increase lung growth in patients diagnosed antenatally with congenital diaphragmatic hernia, have led to focal tracheomegaly from the presence of the device in the developing airway. This results in a large and floppy trachea, which has led to subsequent respiratory difficulties (6, 7).

During normal inspiration there is positive pressure in the airway and negative pressure in the pleural space. During expiration, intra-pleural pressure increases and airway pressure drops as air flow begins, resulting in collapse and possible closure of the tracheal cartilage of a floppy airway (8). This problem is exaggerated during forced expiration or if the patient attempts to increase their expiratory effort, as this will decrease the intra-tracheal pressure more, leading to further collapse and compression of the airway.

Hence patients with obstruction in the upper extra-thoracic airway present with inspiratory stridor, while obstruction in the intra-thoracic part of the airway causes biphasic or an expiratory noise or prolonged expiration on auscultation. In addition, the child may not present until a few months of age, when the obstruction is unmasked by their increased activity and the need for larger tidal volumes as the child grows. Occasionally, the airway problem only comes to light following a respiratory tract infection resulting in increased respiratory effort, or difficulty in intubation with an appropriate size endotracheal tube, or inability to extubate following general anesthesia for a planned surgical procedure. Late presentation at a few months of age does not exclude a congenital lesion.

To ensure that a diagnosis is made earlier it helps to have a high index of suspicion. Consider the possibility of an airway problem and investigate if the following symptoms and signs are present:

recurrent stridor or wheeze

The neonate, who presents with repeated respiratory symptoms, feeding difficulties and recurrent cyanotic episodes, is more likely to have a communication between the airway and esophagus causing recurrent aspiration pneumonia. A history of previous requirement for intubation and mechanical ventilation may provide a clue toward a diagnosis of acquired stenosis, while associated cardiac defect and signs of dysmorphism may suggest a congenital lesion. Repeated failed extubation attempts point toward a diagnosis of airway obstruction due to stenosis and/or malacia. Investigations should therefore be targeted to these possibilities. Patients presenting with cyanotic episodes and life-threatening events should be referred and investigated urgently.

Symptomatic major airway problems are not an uncommon manifestation in preterm babies with chronic lung disease. There has been a recent increase in reports in the literature with earlier recognition due to the ability to investigate the problem (9, 10); as well as an increased occurrence following the use of tracheal occlusive devices in fetuses with congenital diaphragmatic hernia (6, 7).

Simple non-invasive tests are helpful and often provide some clues to the diagnosis, although more invasive tests may often be required to determine the extent and severity of airway involvement. Below are the investigations available to clinicians that can be used in various combinations.

Subsequent management needs to be planned following careful precise assessment of the airway and may need to be highly individualized (21). Not all patients will need surgery following the diagnosis, and some patients can be managed with a “watch and wait” approach, as long as they are putting on weight and do not have life-threatening symptoms. The need for, and type of, intervention depends on the extent and severity of airway involvement, which would often determine how symptomatic the child is.

The outcome of children with tracheal stenosis and tracheomalacia has improved significantly in the last few years. The mortality was previously high with significant morbidity. It was initially reported that the need for ventilation for longer than 14 days and the bronchogram findings of moderate to severe malacia of the trachea and bronchi were predictive of a fatal outcome (43). Review of our patient population, however, showed that length of ventilation or severity of tracheomalacia was not predictive. Figure 9 shows the Kaplan–Meier curve of survival in different diagnostic groups. We found that associated comorbidity was more predictive of mortality, and patients with cardiac problems or who were syndromic had a much poorer outcome than patients who had tracheomalacia associated with trachea-esophageal fistula, as an isolated primary airway problem or from prematurity (44).

Further improvements have occurred with advances in surgical and interventional radiology techniques, intensive care management, and multidisciplinary team working in centralized units (21, 42, 45). Figure 10 shows a reduction in length of ventilation, in addition to a significant reduction in the length of stay in ICU and in hospital. The costs for management per complex airway patient have therefore come down significantly by £51,114 per patient (46). The long-term survival now exceeds 88%, and many patients have a normal quality of life (21).

Stem cell-based tissue-engineered tracheal replacement is an exciting therapeutic option for the future. A decellularized cadaveric tracheal scaffold is seeded with bone marrow mesenchymal stem cells harvested from the recipient. This has been done in 2010 in a child who had tracheal stenosis and failure of surgical repair with erosion of the stent. There is evidence of revascularisation of the graft within a week after surgery and restoration of the respiratory epithelium 1 year later. After 18 months, the graft had biomechanical strength, and the patient has not needed any medical intervention since. His CT scan and ventilation perfusion scan are reported as normal, and he has grown 11 cm in height since the procedure. He has been followed up 6 years posttransplant and now leads a completely normal life (47, 48).

In patients with congenital tracheal stenosis, careful assessment of the airway is of paramount importance to plan further management strategies. We feel that bronchography and flexible bronchoscopy are essential tools for diagnosis, intervention, and follow-up, although echocardiography, computed tomography, and MRI may be important for the evaluation of associated cardiovascular abnormalities. Our current management strategy involves slide tracheoplasty in combination with balloon dilatation and occasionally stenting in cases of recurrent stenosis. Multidisciplinary team working within centralized units is crucial and has reduced the morbidity and cost of managing these patients. Survival rates have risen dramatically, and innovative management strategies will lead to a much brighter outlook for these patients.

QM is the sole author who researched the topic and wrote the entire paper. Some of the radiographs and bronchoscopy pictures have been provided by the other members of the trachea team.

The author is a consultant intensivist working in Great Ormond Street Hospital in the National Health Service. She is a member of the multidisciplinary trachea team of the hospital, although has no additional time or remuneration for being involved in this team.