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.