B. Yuksel

Respiratory morbidity in preschool children born prematurely. Relationship to adverse neonatal events

Respiratory morbidity, recurrent cough and/or wheeze and lung function abnormalities are common even outside infancy in preschool children born prematurely. Throughout the first 5 years of life, adverse neonatal events such as immaturity at birth and a requirement for prolonged respiratory support are significantly associated with positive symptom status. In the older preschool child, however, there is some evidence to suggest that other factors, such as a family history of atopy, may be equally important. The development of recurrent symptoms even at 4 years of age can be predicted accurately from the results of lung function measurements made in infancy, and hopefully such data will facilitate the introduction of effective intervention strategies. Lung function abnormalities are more marked in symptomatic patients and, in older children, seem to reflect increased airway responsiveness rather than having a significant relationship to adverse neonatal events. The hospital readmission rate for respiratory disorders, however, is certainly adversely affected by extremely low birthweight and neonatal chronic lung disease, as well as current symptom status. These data highlight that strategies to reduce extremely premature delivery and its consequences should favourably influence respiratory morbidity in preschool children.

Recurrent respiratory symptoms in the first year of life following preterm delivery

Recurrent respiratory symptoms in the first year of life following preterm delivery were documented in two studies. In the first study a questionnaire was sent to all parents of preterm very low birth weight (VLBW) infants who had been admitted during a six-month period to the Neonatal Intensive Care Unit (NICU) at Kings College Hospital (KCH) and who lived within the local district. Questionnaires were also sent to parents of a control group of infants who were recruited by random selection. All the controls lived locally and were delivered at KCH in the same six-month period as the study group, but were born at 37-41 weeks of gestation and had had no neonatal problems. The questionnaire documented frequency of cough and wheeze, medication and hospital admissions. Recurrent respiratory symptoms (wheeze or wheeze and cough) occurred in 65% of the preterm VLBW infants but only 33% of the controls p less than 0.001. Less than 10% of infants in either group had received bronchodilator therapy. Admission to hospital in both groups was more common amongst children who had recurrent wheeze (p less than 0.01). In the second study all preterm VLBW infants admitted to the NICU in a six-month period were followed prospectively over the first year of life. The nature and frequency of respiratory symptoms and frequency and length of re-admission was documented and related to the duration of neonatal ventilation. Twenty-three of the 44 preterm VLBW infants (53%) followed prospectively had recurrent wheeze and/or cough.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhaled sodium cromoglycate for pre-term children with respiratory symptoms at follow-up

Children born prematurely frequently have recurrent respiratory symptoms at follow-up and benefit from bronchodilator therapy. We have assessed if regular inhaled sodium cromoglycate would reduce this respiratory morbidity and need for bronchodilator therapy. Sixteen symptomatic children (median gestational age 29 weeks, post-natal age 15 months) were entered into a randomized double-blind, placebo-controlled trial. In two 3-week periods, the patients received either placebo or sodium cromoglycate (5 mg) as one puff q.d.s. from an inhaler via a coffee cup. Parents recorded their childs symptoms and need for bronchodilator therapy throughout and lung function was assessed by measurement of functional residual capacity (FRC) at the beginning and end of each 3-week period. The symptom score was reduced by 49% in the active compared to the placebo period (P less than 0.01) and bronchodilator was taken on a mean of 2.9 days per infant in the active period compared to 7.9 days in the placebo period (P less than 0.01). There was a significant improvement in FRC in ten of 16 patients over the active period but only in two infants over the placebo period (P less than 0.01). We conclude regular inhaled sodium cromoglycate is useful prophylaxis for symptomatic pre-term children.

Ipratropium bromide for symptomatic preterm infants.

Twelve preterm infants, median gestational age 31.5 weeks, were entered into a randomised, placebocontrolled trial of bronchodilator therapy. Their postnatal age was a median of 17.5 months and all suffered from recurrent respiratory symptoms. The infants received either inhaled placebo or 40 μg of ipratropium bromide (active therapy) three times a day utilising a coffee cup as a spacer device. Each therapy was administered for 2 weeks. The symptom score during the active period was reduced by 59% compared to the placebo period (P<0.01) and this was associated with 38% improvement in lung function in the active period compared to a 20% change in functional residual capacity over the placebo period (P<0.01). We conclude inhaled ipratropium bromide appears to be an effective treatment for symptomatic infants at follow up.

Chronic respiratory morbidity following premature delivery – prediction by prolonged respiratory support requirement?

Abstract Neonatal chronic lung disease (CLD) is usually diagnosed if an infant remains oxygen dependent beyond 36 weeks postconceptional age (PCA). Our aim was to determine whether a shorter duration of respiratory support accurately predicted subsequent respiratory morbidity. A total of 103 infants, median gestational age 29 weeks (range 23–35), were followed prospectively for 5 years. They had a birth weight of <1500 g or, if a birth weight of between 1500 and 2000 g, had required neonatal ventilatory support. Parents completed diary cards; their child had positive symptom status if, in any one year, they coughed and/or wheezed on at least 3 days per week for a 4-week period or for at least 3 days following each upper respiratory tract infection. Subsequent respiratory morbidity, positive symptom status in years 1 and 2 or all 5 pre-school years, was related to various definitions of prolonged respiratory support: intermittent positive pressure ventilation dependence >7 days; oxygen dependence >28 days and oxygen dependence >36 weeks PCA. In years 1 and 2, 25 children were symptomatic and 22 in all 5 years. The patients with subsequent respiratory morbidity were distinguished from those without by requiring longer respiratory support (P < 0.05). Logistic regression analysis demonstrated only oxygen dependence beyond 28 days was independently related to subsequent respiratory morbidity (P < 0.01). The positive predictive values and likelihood ratios (95% confidence intervals) for positive symptom status in all 5 years were for intermittent positive pressure ventilation >7 days 35% (16–53) and 19.5 (1.01–3.76), for oxygen dependency >28 days 42% (23–61) and 2.20 (1.45–5.02) and for oxygen dependency >36 weeks PCA 35% (13–58) and 1.67 (0.65–4.31). Conclusion Oxygen dependency at 28 days of age remains a useful criterion on which to diagnose “neonatal” chronic lung disease.

Respiratory morbidity in young school children born prematurely--chronic lung disease is not a risk factor?

AbstractChildren born prematurely and recruited into a prospective follow up study were examined at 5 years of age. Our aim was to determine actiological associations of respiratory symptoms in such children and in particular, to determine the importance of severe chronic lung disease (CLD, oxygen dependence beyond 36 weeks post conceptional age). Respiratory status was documented from parental history in 103 children of median gestational age 29 weeks (range 23–35), 17 of whom had suffered from severe CLD. In 90 of the 103 children lung function had been assessed at 1 year of age. Regression analysis revealed that neither severe CLD nor other perinatal variables, but only a family history of atopy, significantly related to a positive symptom status. A high airways resistance at 1 year also significantly related to positive symptom status.ConclusionReduction in severe CLD (oxygen dependence beyond 36 weeks postconceptional age) may make relatively little impact on respiratory morbidity in young school children born prematurely.

Comparison of the effects on lung function of two methods of bronchodilator administration

The aim of this study was to assess if administration of bronchodilator via a metered dose inhaler (MDI), rather than by a nebulizer, avoided the early paradoxical deterioration in lung function but, resulted in equally effective late bronchodilation. Fifteen children were studied at a median postnatal age of 9 months (range 9-18), all had been born prematurely at a median gestational age of 27 weeks (range 23-31). Lung function was measured by plethysmography before and 10 min after normal saline and 5 and 15 min after salbutamol given via an MDI and a nebulizer in random order. At 5 min, compared to baseline values, airways resistance (RAW) deteriorated by 16% after nebulized salbutamol but improved by 3% following salbutamol by the MDI (P < 0.03). At 15 min RAW improved by 14% following nebulized salbutamol and 15% after salbutamol via the MDI, there was no significant difference in the magnitude of bronchodilation between the two methods of administration. Our results therefore suggest, that as the early paradoxical deterioration in lung function is usually avoided by administering salbutamol via an MDI, this should be the preferred method of administration.

Neonatal respiratory support and lung function abnormalities at follow-up

We have investigated if respiratory distress syndrome (RDS) treated by an increased inspired oxygen concentration, rather than mechanical ventilation, was associated with impaired lung function at follow-up and/or an increase in respiratory symptoms. Thoracic gas volume (TGV) and airways resistance (RAW) were measured in eight pre-term infants (median gestational age 29 weeks) at 6 and 12 months of age. The infants had suffered from RDS but had not required mechanical ventilation. Their results were compared to 16 other infants, matched for gestational age; eight who had required ventilation in the neonatal period and eight who had had no RDS. In all three groups the occurrence of respiratory symptoms was recorded. The lung function of the infants requiring oxygen in the neonatal period was similar to those who had not suffered from RDS, but their airways resistance was significantly lower at 6 but not 12 months than that of infants ventilated in the neonatal period (P less than 0.05). There was no significant difference in recurrent respiratory symptoms between the three groups although a greater proportion of the infants ventilated in the neonatal period were symptomatic in the first 6 months of life. These results suggest that oxygen therapy alone does not result in an impairment of lung function which is independent of the effect of prematurity.

Respiratory function at follow-up after neonatal surfactant replacement therapy

Respiratory function was assessed at a median of 7 months (range 6-12) in 17 preterm infants who, in the neonatal period, had been entered into a multi-centre randomized placebo-controlled trial of prophylactic surfactant replacement therapy. Seven infants (median gestational age 28 weeks) received surfactant and the remaining ten infants (median gestational age 27 weeks) placebo. Respiratory function was assessed by measuring functional residual capacity (FRC), thoracic gas volume (TGV) and airways resistance (RAW). Specific conductance (SGAW) was calculated from RAW and TGV. There was no significant difference in FRC or TGV between the two groups. RAW, however, was significantly lower in the surfactant (median 41, range 21-48 cmH2O l-1 s-1) compared to the placebo group (median 57, range 40-68 cmH2O l-1 s-1), P < 0.05 and SGAW significantly higher in the surfactant (median 0.136, range 0.063-0.289 l cmH2O-1 s-1) compared to the placebo group (median 0.081, range 0.062-0.134 l cmH2O-1 s-1), P < 0.05. These results suggest that surfactant replacement therapy improves lung function at follow-up.

Inhaled ipratropium bromide and terbutaline in asthmatic children

Inhaled bronchodilator therapy in young asthmatic children reduces symptoms and improves lung function. After a single dose of therapy, however, lung function may still be abnormal, as evidenced by an elevated function residual capacity (FRC). The aims of this study were to assess if a second dose of bronchodilator therapy resulted in further improvement in lung function and to determine whether additional therapy was more effective if given as a second dose of a beta-adrenergic agonist or if instead an anticholinergic was used. Twenty-one asthmatics (median age 7.5 years) received in random order on two separate occasions, 1 week apart, either two doses of terbutaline (500 micrograms) or terbutaline plus ipratropium bromide (20 micrograms). FRC and peak expiratory flow rate (PEFR) were measured immediately prior to and then 20 min after each dose of bronchodilator therapy. In the group, overall FRC and PEFR improved after the first and second dose of bronchodilator, regardless of regime used, the response to the second dose, however, was smaller than the first dose. There was no significant difference overall between the two regimes in baseline FRC or PEFR, or FRC and PEFR measured after each dose of bronchodilator. Eight children failed to show a significant change in FRC following two doses of terbutaline, but seven of these eight did have a significant change in FRC in response to the combination of terbutaline and ipratropium bromide. We conclude that a second dose of bronchodilator therapy does further improve lung function. Our results suggest the more efficacious regime consists of a combination of single doses of ipratropium bromide and terbutaline.