Treatment of Wheezing in Preterm Infants and Children
Medications used to treat wheezing or asthma such as BDs and ICS in term
infants and children have frequently been used in preterm infants and
children [40]. However, as discussed above the underlying
pathophysiology of wheezing in preterm children is different from that
of asthma. For example, FeNO tends to be low in BPD, whereas it is
elevated in children with atopic asthma [41]. Furthermore, many
children with BPD can have tracheobronchomalacia, which could worsen
with BD therapy [43]. The immune response to viral infection is
altered in preterm infants and children [9-11]. In addition, some
medications used to treat BPD, such as diuretics, may have effects on
airway resistance, which is increased in the setting of wheezing
[44].
Follow up studies of preterm infants have shown a high prevalence of BD
use after discharge from the NICU, but there are few studies that have
assessed its use as chronic daily therapy in BPD. Yuksel, et al
administered terbutaline or placebo for 2 weeks to 10 preterm infants
with a mean age of 12.5 months using a non-randomized, cross-over study
design [45]. The primary outcome measures were a self-designed,
non-validated symptom score and functional residual capacity (FRC)
measured by helium dilution. They found that terbutaline therapy was
associated with a significant improvement in symptom scores, but
paradoxically led to an increase in FRC. In a study of older preterm
children given daily inhaled terbutaline for 4 weeks, no significant
change in the forced expiratory volume in 1 second (FEV1) was observed,
although peak expiratory flow did increase significantly.
Although data supporting the effect chronic daily inhaled BD therapy on
improving lung function are lacking, there have been numerous studies of
the effects of single dose BD therapy on lung function, and between
24-97% of preterm children have demonstrated a significant BD response
as measured by improvement in FEV1 [46]. Taken together, these data
suggest that chronic daily BD therapy is probably not beneficial in
children with BPD. However, intermittent use of short-acting beta
agonists may have a role in treatment of acute wheezing episodes in this
patient population.
ICS are commonly used to treat asthma in children, but their role in
preventing wheezing in preterm infants and children is less clear.
Randomized clinical trials of ICS therapy in preterm children have been
conducted in both preterm infants and children [47-50].
Unfortunately, the strength of these studies has been limited by small
study cohorts and the lack of standardized, validated clinical symptom
scores. Overall, these studies have failed to show a consistent effect
of ICS therapy on improving clinically important outcomes, and routine
use of ICS in preterm children is not indicated. However, ICS may be
helpful in preterm children with a history suggestive of asthma.
Diuretics are commonly administered to preterm infants in the NICU, and
both furosemide and thiazide/spironolactone combination therapy have
demonstrated in RCTs to increase pulmonary compliance and reduce airway
resistance [51]. Long-term use of these medications, especially
furosemide, can be associated with several side effects, including
nephrolithiasis, hearing loss, and metabolic bone disease [52].
Diuretic therapy in preterm infants after discharge from the NICU has
not been shown to reduce the risk of wheezing or other respiratory
symptoms. They may be useful though for acute management of wheezing and
hypoxemia in infants with BPD.