Tracheomalacia, Bronchomalacia, and Tracheobronchomalacia
The central airway is a dynamic structure that changes both size and shape during the respiratory cycle. The extent of airway collapse depends both on the rigidity of the airway and the pressure applied across the airway wall. The airway of neonates with BPD, does not undergo the natural maturation process and is hence less rigid, and this propensity to collapse can be exacerbated by damage to the trachea from positive pressure ventilation, which is frequently necessary in the management of BPD. Further, patients with BPD have increased airway resistance and often utilize accessory muscles for exhalation, which can increase transmural airway pressure for the intrathoracic airway. Consequently, dynamic pathologies such as tracheomalacia (TM), bronchomalacia (BM), and tracheobronchomalacia (TBM) are quite common in this population.
Historically, the diagnosis of TBM in neonates has required either direct visualization with bronchoscopy (Fig 1A & 1D) or imaging with ionizing radiation such as fluoroscopy or computed tomography(Fig 1B & 1E) (16-21) and is defined based on the percent of airway collapse during spontaneous respiration. There is currently no widely accepted, standardized method for the evaluation of TBM; however, most experts agree that dynamic collapse during quiet breathing by more than 50% is abnormal.(22) Unfortunately, relying solely on airway collapse does not take the pressure applied across the airway into account when evaluating airway dynamics. Lack of a standardized technique and inability to account for patient effort may in part contribute to variability in the diagnosis of TBM, which can be seen in neonates, even under the same sedation.(23) In an effort to obtain and objective, purely quantitative measure and avoid radiation and the need for sedation, ultrashort echo-time (UTE) MRI with respiratory gating has been recently been utilized to evaluate TM in neonates with BPD (Fig 1C & 1F).(24, 25) While this technique exposes neonates to minimal risk and permits evaluation of airway dynamics in entire patient populations, UTE MRI is not yet widely available.
Because most methods for assessing airway dynamics expose children to sedation, ionizing radiation, or both, these evaluations are only performed in select patients. Thus, the true prevalence of TBM in BPD is unknown; however, the prevalence is estimated to be between 10-48%.(16-20) Further, infants with severe BPD are more likely to develop TBM and have greater variability and severity of dynamic collapse than children with mild or moderate premature lung disease.(25)
Dynamic collapse of the central airways is correlated with increased respiratory morbidity in patients with BPD, both during the neonatal period and toddler years. Clinically, patients with TBM can present with mild symptoms such as cough, wheezing, noisy breathing or more severe symptoms such as cyanotic spells and inability to wean respiratory support.(26, 27) Neonates with BPD and TBM are treated for longer periods of time with invasive mechanical ventilation an undergo more surgical interventions such as tracheotomy and gastrotomy during the initial hospitalization.(17, 21) The net impact for patient with BPD and TBM is to be hospitalized for three weeks longer than patients with BPD alone, which is similar to the impact of necrotizing enterocolitis. At the time of hospital discharge, patients with TBM are more likely to be technology dependent and treated with multiple pharmacologic therapies.(17) Following discharge, infants with TBM have a more than 60% increased frequency of rehospitalization during the first year of life.(28) Despite the marked impact of central airway collapse during the neonatal and toddler periods, no studies have assessed the implications of dynamic central airway obstruction in BPD nor the natural progression of airway dynamics throughout childhood.
Typically, TBM is self-limited and thought to resolve by the second year of life without intervention.(29, 30) Treatment depends on the severity and location of airway collapse and, more importantly, the severity of clinical symptoms. While no studies have rigorously evaluated therapeutics for TBM in patients with BPD, treatment strategies for TBM in general include pharmacotherapy, positive pressure ventilation, and surgical intervention.
Pharmacotherapy is primarily aimed at increasing trachealis tone and decreasing tracheal compliance. Treatment with cholinergic agents such as bethanechol reduce tracheal compliance in neonatal animal models (31) and improve respiratory mechanics and symptoms in infants and children with TBM.(32, 33) Inhaled ipratroprium bromide in low doses blocks type 2 muscarinic receptors, which potentiate acetylcholine activity in the neuromuscular junction and stimulate contraction of tracheal smooth muscle; however, antagonistic effects of type 3 muscarinic receptors dominate at high doses and result in relaxation of airway smooth muscle, which could exacerbate tracheal collapse.(34) Similarly, treatment with albuterol relaxes airway smooth muscle and can impair respiratory mechanics in infants with TBM in the absence of known lung disease, (32) but, in patients with severe BPD, nearly two-thirds of patients have a positive bronchodilator response based on pulmonary function testing during the neonatal period. (35) Consequently, albuterol can be considered with caution for treatment in patients with BPD, even those with known TBM.
Non-invasive continuous positive airway pressure (CPAP) is frequently used for respiratory support in neonates with BPD, and may have added benefits in the management TBM. CPAP serves as a pneumatic stent which decreases airway resistance, reduces respiratory work, and raises lung volumes in infant with TBM. (15, 36, 37) Positive airway pressure can also be provided invasively via an endotracheal tube or tracheostomy tube, and the artificial airway can bypass the collapsible segment of airway.
Because dynamic collapse is typically identified throughout the airway rather than in a focal segment of the trachea; (16) prolonged positive pressure may be necessary to manage both the proximal TM and more distal BM as well as the parenchymal lung disease. Consequently, tracheotomy is the primary surgical intervention for treatment of dynamic airway obstruction in patients with BPD. Aortopexy involves pulling the aorta anteriorly off of the trachea and has historically been used to treat focal TM in children. While aortopexy results in symptomatic relief in a majority of children, the benefits seem to be related to creating more space in the tracheal lumen by relieving vascular compression rather than treating the TM. (38) More recently, posterior tracheopexy has shown promise in treating TM in children. By suturing the posterior membrane of the trachea to the anterior longitudinal ligament of the spine, posterior tracheopexy can prevent dynamic collapse of the trachea and improve severe symptoms such as the need for mechanical ventilation and cyanotic spells in infants with esophageal atresia.(26, 39) Despite the improvement in other diseases, the efficacy of aortopexy and posterior tracheopexy has yet to be established for the management of patients with BPD and TBM.