Nutritional Status in Childhood as a Prognostic Factor in Patients with Cystic Fibrosis.

INTRODUCTION: There is a strong association between cystic fibrosis and malnutrition, mainly because of the higher energy needs combined with lower intake. There is also a well-established correlation between good nutritional status and better lung function. To date, however, there are no studies examining nutritional status in childhood and adult lung function. To respond to this need, this innovative study explored the long-term correlations between nutritional status in childhood and lung function in adulthood for the same patient population. METHODS: A retrospective patient file study was conducted to identify putative correlations between nutritional status in childhood and lung function in adulthood. The medical archives at Sheba Medical Center were examined for a period of 31 years between 1986 and 2017 for age, gender, mutations, pancreatic sufficiency or insufficiency (PI/PS), sputum cultures, cystic fibrosis related diabetes, body mass index (BMI) at the age of 10, and FEV1 at 20 and 30 in patients who underwent or did not undergo lung transplantation. RESULTS: The database was composed of the records of sixty-five patients, thirteen of whom underwent lung transplantation. The correlations (R²) between BMI at age of 10 years and FEV1 at the age of 20 and 30 years were 0.35 and 0.28, respectively, p < 0.001. A BMI of lower than - 0.75 at the age of 10 emerged as a risk factor for lung transplantation (OR 3.42 p = 0.023) and had a negative predictive value of 90%. Kaplan-Meier survival curve showed significant lower lung transplantation rate in the group of BMI z score higher than - 0.75 at the age of 10 years. Logistic regression found nutritional at the age of 10 years as a dominant risk factor for lung transplantation. CONCLUSIONS: This study reports a clear, significant and important correlation for the first time between nutritional status in childhood and lung function for the same patients at adulthood. Hence, nutritional status sets a clear trajectory and should be treated aggressively. The findings emphasize the importance of new-born screening and early implementation of nutritional guidelines for cystic fibrosis patients.

An interactive computer-animated system (SpiroGame) facilitates spirometry in preschool children.

Although airway disease in preschool children is common, standard spirometry is limited by the level of cooperation. We evaluated a computer-animated system (SpiroGame) aimed at improving children's performance in spirometry. SpiroGame includes a commercial pneumotachograph (ZAN100; ZAN Messgeraete GmbH, Oberthulba, Germany) and games teaching tidal breathing and all steps of an FVC maneuver. SpiroGame was compared with commercial flow-targeted candle-blowing software (MasterLab, Jaeger, Germany), and with extrapolated predicted values. Of 112 children aged 3 to 6 yr, 10 refused spirometry and 102 proceeded to FVC games and were randomized to initially perform either SpiroGame or candle-blowing. Training lasted 5 to 10 min for SpiroGame and 3 to 7 min for candle-blowing. Acceptable spirometry was performed by 69 of 102 children with SpiroGame and 48 of 102 with candle-blowing (p = 0.005). Order did not affect success. Acceptable FEV(1) maneuvers were achieved by 55 children with SpiroGame and two children with candle-blowing. The intrasubject coefficient of variation was 4.0% for FVC and 3.3% for FEV(1) with SpiroGame. A premature expiratory break occurred in 41 subjects with candle-blowing and in six with SpiroGame. FEV(0.5) could be measured with both systems. FVC and maximal midexpiratory flow at 50% of FVC (MMEF(50)) values were similar, whereas peak expiratory flow was higher with candle-blowing. In 39 healthy children, most parameters with SpiroGame were similar to extrapolated normal values. We conclude that an interactive computer-animated system facilitates successful spirometry in preschool children.

Comparison of respiratory inductance plethysmography with thoracoabdominal compression in bronchial challenges in infants and young children.

Respiratory inductance plethysmography measuring thoracoabdominal asynchrony (TAA) has been claimed to be a useful tool for measuring changes in airway resistance in infants. In this study we evaluated the response to methacholine by thoracoabdominal compression and respiratory inductance plethysmography. Seventeen infants (mean age, 13.1 +/- 4.7 mo) with recurrent episodes of cough or wheeze underwent bronchial challenge with inhaled methacholine. Lung function was evaluated by measuring maximal expiratory flow at resting lung volume (VmaxFRC), and the degree of TAA was measured by phase angle (theta). Methacholine was inhaled for 1 min during tidal breathing using increasing doubling concentrations until a fall of at least 40% in VmaxFRC was achieved (final concentration). All infants responded to the final concentration of methacholine by a significant fall in VmaxFRC (from 31 +/- 10 to 12 +/- 5 ml/s/kg, p < 0.001). All but one infant responded to methacholine at the final concentration with a significant increase in phase angle (median theta increased from 11.7 to 31.7 degrees, p < 0.001). In two other infants there was an early response in theta compared with the response in VmaxFRC. Phase angle increase after methacholine was expressed as Z-scores (the difference between postmethacholine theta and postbuffer theta divided by the standard deviation of postbuffer theta). An increase of at least 2.0 Z-scores in theta was observed at the same concentration of methacholine when VmaxFRC fell by at least 40% in 15 of the 17 infants (88%). We conclude that respiratory inductance plethysmography is a sensitive method to measure bronchial reactivity to methacholine in most of the infants studied (14 of 17, 82%). A concentration of methacholine causing an increase in theta of at least 2.0 standard deviations above baseline is equivalent to the concentration causing a 40% fall in VmaxFRC.

Computerized respiratory muscle training in children with Duchenne muscular dystrophy.

The present study describes the use of simple video games for a 5-week regimen of respiratory muscle training in 15 patients with Duchenne muscular dystrophy (DMD) at various stages of the disease. The games were re-arranged to be operated and driven by the respiratory efforts of the patient and to incorporate accurate ventilation and time measurements. Improvement in respiratory performance was determined by maximum voluntary ventilation (MVV), maximal achieved ventilation (VEmax) during a progressive isocapnic hyperventilation manoeuvre (PIHV) and the PIHV duration. The actual training period was 23 +/- 4 days (mean +/- S.D.) at ventilatory effort of 46 +/- 6% MVV, for 10 +/- 3 min day-1. Patients with moderate impairment of lung function tests (LFT) showed an improvement in MVV, VEmax, and duration of PIHV of 12 +/- 7% (p < 0.02), 53 +/- 25% (p < 0.001) 57 +/- 21% (p < 0.01), respectively. Improvements correlated with actual training time and ventilation level, %MVV, but negatively correlated with years of immobilization and with the initial MVV. We conclude that computerized respiratory games may be applied for breathing exercises and may improve respiratory performance in recently immobilized children with DMD who have moderate impairment of LFT.

Comparison of airway resistance and total respiratory system resistance in infants.

Airway resistance (Raw) can be measured throughout the respiratory cycle by whole body plethysmography. Total resistance of the respiratory system (Rrs) can be measured from the relaxed expiration that follows end inspiratory occlusion. The purpose of this study was to compare the two methods in normal infants and in infants with airway obstruction of different types and severity. Fifteen infants with essentially normal lungs aged 24.6 +/- 18.0 (SD) wk, nine infants with congenital stridor aged 36.0 +/- 17.3 wk, and eleven wheezy infants aged 20.1 +/- 11.3 wk had simultaneous measurements of Raw and Rrs. Rrs was similar to Raw both during inspiration and expiration in the normal infants, to all expiratory Raw in those with congenital stridor, and to all inspiratory and early expiratory Raw in the wheezy infants. Raw was markedly and significantly higher than Rrs during mid and late inspiration in infants with congenital stridor and during late expiration in the wheezy infants. We conclude that Rrs is a good estimate of Raw in normal infants and of early expiratory Raw in all infants. In infants with airway obstruction, Rrs does not reveal the dynamic changes in Raw during tidal breathing, nor can it differentiate between infants with upper and lower airway obstruction.

Corticosteroids do not affect the clinical or physiological status of infants with bronchiolitis.

The treatment of infants aged 1.5-11.0 months suffering from acute bronchiolitis with a combination of inhaled albuterol and systemic corticosteroids or inhaled albuterol and placebo was compared in 50 infants in a double blind study. The mean initial clinical score and the rate of improvement was similar in the two groups. The mean +/- SD hospital stay was 5.0 +/- 1.2 days for the steroid group and 5.2 +/- 1.7 days for the placebo group. Lung function was measured in 14 infants (7 from each group) and showed evidence of increased lung volumes and severe airway obstruction in the acute stage (the mean values for the steroid group were: TGV, 31 mL/kg; SGaw, 0.104 L/s.cmH2O; VmaxFRC, 12.9 mL/s/kg; for the placebo group: TGV, 35 mL/kg; SGaw, 0.104 L/s.cmH2O; VmaxFRC, 8.5 mL/s/kg) which had improved 2-4 weeks later (steroid group: TGV, 25 mL/kg; SGaw, 0.168 L/s.cmH2O; VmaxFRC, 21.6 mL/s/kg; -placebo group: TGV, 24 mL/kg, SGaw, 0.198 L/s.cmH2O, VmaxFRC, 17.5 mL/s/kg). There were no significant differences of thoracic gas volume, specific airway conductance, and forced expiratory flow at resting lung volume between the two groups, either in the acute or convalescent stages. We conclude that corticosteroids do not change the rate of clinical improvement in acute bronchiolitis, nor do they effect lung function 2-4 weeks later.

Expiratory volume clamping: a new method to assess respiratory mechanics in sedated infants.

During breathing under sedation via a two-way valve, airflow (V), volume (delta V), and airway pressure (P) were recorded in eight normal (N) infants, seven with reversible obstructive airway disease (ROAD), and seven with chronic lung disease (CLD). Intermittently, expiratory volume clamping (EVC) was applied, involving selective occlusion of the expiratory valve for three to five breaths. The latter produced cumulative increases in delta V that, due to progressive recruitment of the Hering-Breuer reflex, were accompanied by increasing expiratory plateaus in P (i.e., apneas). The resultant passive inflation delta V-P relationships were closely approximated by the expression: delta V = aP2 + bP + c, wherein a represented the pressure-related changes in chord compliance (Crs), b the Crs at P = 0, and c the difference between the dynamic end-expiratory and relaxation volumes of the respiratory system. Relative to N, the ROAD and CLD infants had significantly reduced weight-specific values of a/kg, their b/kg values were increased, whereas the c/kg measurements did not significantly vary. Moreover, for each subject we determined the net Crs/kg obtaining at P = 20 cmH2O (i.e., Crs20/kg), an estimate of the net deflation compliance; the passive respiratory time constant (tau rs) based on the slope of the expired delta V/V relationship; and the respiratory system conductance (Grs/kg). Relative to N, the mean Crs20/kg was significantly reduced only in the infants with CLD and, due to increases in tau rs, both patient groups depicted significantly diminished values of Grs/kg, suggesting the presence of airways obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

A non-invasive method for measuring inspiratory muscle fatigue during progressive isocapnic hyperventilation in man.

Eleven normal adults each performed a ten minute progressive isocapnic hyperventilation (PIHV) test in which ventilatory levels were increased every two minutes. All subjects exhibited mechanical fatigue by failing to maintain the target of 80% of maximum voluntary ventilation (MVV). The mean ventilation at this level was 67.5 +/- 1.4% MVV. This fatigue was accompanied by a fall in transdiaphragmatic pressure. During the test the EMG of the sternomastoid (SM) was monitored by surface electrodes and was analyzed using fast-fourier transform. The centroid frequency (Fc) fell as ventilation increased, and correlated negatively with the inability to achieve target ventilation(r = -0.99, p less than 0.015). Five subjects performed the test while the diaphragmatic EMG was recorded from an oesophageal electrode (DIes) and from surface electrodes (DIs). The Fc of DIes fell with increasing ventilation levels (r = -0.95, p less than 0.05) and there was a correlation between the Fc changes of both DIes and the SM (r = -0.92, p less than 0.001). The Fc of DIs did not correlate with either mechanical performance or the Fc of DIes, because of contamination of surface signals by signals from expiratory muscles. It is concluded that the PIHV along with surface monitoring of EMG activity from the sternomastoid can serve as a non-invasive method for evaluating inspiratory muscle fatigue.