Tidal Breathing Measurements at Discharge and Clinical Outcomes in Extremely Low Gestational Age Neonates.

RATIONALE: The relationship between respiratory function at hospital discharge and the severity of later respiratory disease in extremely low gestational age neonates is not well defined. OBJECTIVES: To test the hypothesis that tidal breathing measurements near the time of hospital discharge differ between extremely premature infants with bronchopulmonary dysplasia (BPD) or respiratory disease in the first year of life and those without these conditions. METHODS: Study subjects were part of the PROP (Prematurity and Respiratory Outcomes Program) study, a longitudinal cohort study of infants born at less than 29 gestational weeks followed from birth to 1 year of age. Respiratory inductance plethysmography was used for tidal breathing measurements before and after inhaled albuterol 1 week before anticipated hospital discharge. Infants were breathing spontaneously and were receiving less than or equal to 1 L/min nasal cannula flow at 21% to 100% fraction of inspired oxygen. A survey of respiratory morbidity was administered to caregivers at 3, 6, 9, and 12 months corrected age to assess for respiratory disease. We compared tidal breathing measurements in infants with and without BPD (oxygen requirement at 36 wk) and with and without respiratory disease in the first year of life. Measurements were also performed in a comparison cohort of term infants. RESULTS: A total of 765 infants survived to 36 weeks postmenstrual age, with research-quality tidal breathing data in 452 out of 564 tested (80.1%). Among these 452 infants, the rate of postdischarge respiratory disease was 65.7%. Compared with a group of 18 term infants, PROP infants had abnormal tidal breathing patterns. However, there were no clinically significant differences in tidal breathing measurements in PROP infants who had BPD or who had respiratory disease in the first year of life compared with those without these diagnoses. Bronchodilator response was not significantly associated with respiratory disease in the first year of life. CONCLUSIONS: Extremely premature infants receiving less than 1 L/min nasal cannula support at 21% to 100% fraction of inspired oxygen have tidal breathing measurements that differ from term infants, but these measurements do not differentiate those preterm infants who have BPD or will have respiratory disease in the first year of life from those who do not. Clinical trial registered with www.clinicaltrials.gov (NCT01435187).

Measurement of single breath-hold carbon monoxide diffusing capacity in healthy infants and toddlers.

We describe a method for measuring carbon monoxide diffusing capacity (DL(CO)) and alveolar volume (V(A)) in sleeping infants, using a single 4-sec breath-hold technique. The breath-hold maneuver is obtained by inducing a respiratory pause of the respiratory system. Several inflations of the respiratory system with room air to a lung volume with an airway pressure of 30 cmH2O (V30) inhibit inspiratory effort. The respiratory system is then inflated with a test gas containing helium and a stable isotope of carbon monoxide (C18O), and a respiratory pause is maintained for 4 sec and followed by passive expiration to functional residual capacity. Concentrations of helium and C18O are continuously measured with a mass spectrometer. Twelve healthy infants between 6-22 months of age were evaluated. For 9 of 12 subjects, duplicate measurements of alveolar volume at 30 cmH2O (V(A30)) and DL(CO) were within 10%, which are the recommendations for older children and adults. Among these 9 subjects, values of V(A30) and DL(CO) increased with increasing body length (r2 = 0.82 and 0.79, respectively). The remaining 3 subjects had two values within 10-15%. Measurement of V(A) and DL(CO) with the single breath-hold technique at an elevated lung volume offers the potential to assess growth and development of the lung parenchyma early in life.

Parental smoking and airway reactivity in healthy infants.

Parental tobacco smoking is associated with lower airway function and an increased incidence of wheezy respiratory illnesses in infants. We evaluated in 76 healthy infants whether exposure to parental tobacco smoking was associated with airway hyperreactivity, which could contribute to lower airway function and the increased wheezy illnesses. Airway function was measured using the raised-volume rapid thoracic compression technique, and airway reactivity was assessed by methacholine challenge (0.015-10 mg/ml), which was stopped for a more than 30% decrease in forced expiratory flow (FEF)(75) or the final dose with a less than 30% decrease. Parental tobacco smoking was associated with lower baseline airway function (FEF(50), 600 vs. 676 ml/second, p < 0.04; FEF(25-75), 531 vs. 597 ml/second, p < 0.05). Infants exposed to tobacco smoking were approximately half as likely to develop a more than 30% decline in FEF(75) at any given methacholine dose (hazard ratio = 0.4, p = 0.001). In addition, a history of asthma in an extended family member increased the likelihood that an infant would develop a more than 30% decline in FEF(75) (hazard ratio = 1.7, p = 0.04). We conclude that exposure to parental smoking is associated with lower airway function but not increased airway reactivity; however, family history of asthma is associated with heightened airway reactivity.

Sensitivity of spirometric measurements to detect airway obstruction in infants.

We evaluated the ability of forced expiratory flow volume curves from raised lung volumes to assess airway function among infants with differing severities of respiratory symptoms. Group 1 (n = 33) had previous respiratory symptoms but were currently asymptomatic; group 2 (n = 36) was symptomatic at the time of evaluation. As a control group, we used our previously published sample of 155 healthy infants. Flow volume curves were quantified by FVC, FEF50, FEF75, FEF25-75, FEV0.5, and FEV0.5/FVC, which were expressed as Z scores. All variables except FVC had Z scores that were significantly less than zero and distinguished groups 1 and 2 with progressively lower Z scores. The mean Z scores of the flow variables (FEF50%, FEF75%, and FEF25-75%) were more negative than the Z scores for the timed expired volumes (FEV0.5 or FEV0.5/FVC) for both groups. In general, measures of flow identified a greater number of infants with abnormal lung function than measures of timed volume; FEF50 had the highest performance in detecting abnormal lung function. In summary, forced expiratory maneuvers obtained by the raised volume rapid compression technique can discriminate among groups of infants with differing severity of respiratory symptoms, and measures of forced expiratory flows were better than timed expiratory volume in detecting abnormal airway function.