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.