Vmax FRC Research Articles

PS-176 Development Of Lung Function And Respiratory Morbidity During Infancy In Relation To Severity Of Bpd

Background Development of lung function over time in relation to BPD severity, clinical symptoms, and neonatal risk factors have not been studied in detail. Aim To compare outcomes of infant spirometry in preterm children with variable severity of BPD (levels 1–3) and correlate these to neonatal characteristics and airway symptoms during first 2 years of life. Methods Neonatal data and clinical records from 53 preterm children (weeks 23–30) with BPD (mild, moderate, and severe) were compared with results of two follow-up infant spirometries (at 3 and 18 months corrected age). Respiratory function was assessed during sedation with tidal forced expirations for VmaxFRC according to standardised procedures. Results Mean values of VmaxFRC z-score showed impaired lung function for all stages of BPD both at 3 and 18 months. Vmax FRC was significantly lower (p = 0,017) among children with moderate-severe BPD compared to mild BPD at the second follow-up. There was a significant correlation between VmaxFRC and birth weight (p = 0,004), but not to gestational age or to any specific neonatal complication. In the follow-up, 60% of the children experienced recurrent symptoms of airway obstruction, evaluated as regular use of inhaled corticosteroids or montelukast, and this incidence was significantly higher among the moderate and severe group (p = 0,007). Conclusion Severity of BPD, in parallel to birth weight, correlates to impairment of lung function during first years of life and patient’s need for anti-inflammatory treatment of the airways. Lung function testing is a useful tool for identifying the BPD patients with special needs for follow-up.

WS23.5 Clinical importance of homozygous R117C (c.349C>T) CFTR mutation

Objectives: The CFTR2 Database considers the class IV CFTR mutation R117C (c.349C>T) to be a disease causing mutation. However, the clinical importance is difficult to determine due to its rareness. This report describes the first case of R117C homozygosity, by maternal uniparental isodisomy (UPD) causing cystic fibrosis (CF) and Silver–Russell syndrome. Methods: Clinical description, genetic diagnosis, nasal potential difference (NPD). Results: A 17 months old boy was referred to our CF Centre as a part of the investigation of failure to thrive. Height and weight was within normal variation at birth but decreased to −4SD. The history revealed recurrent upper respiratory tract infections, but no pneumonias, normal stools. Exams showed: Sweat Cl− (Gibson): 54 and 64mmol/L, chest radiogram: bronchial thickening, pulmonary function test: Vmax FRC 275 (+0.2 SD), anti-S. aureus and P. aeruginosa: negative, F-chymotrypsine and -elastase: normal. DNA sequence analysis showed that the mother was a carrier of R117C (IVS-8 7T). No sequence change could be detected in the father. Microsatellites covering chromosome 7 showed maternal UPD of chromosome 7. NPD showed borderline pathology. Patient outcome up to 6 years of age: Sweat Cl−: 92 and 75mmol/L. Chest radiogram: bronchial thickening w/o bronchiectasis. Pulmonary function test: Vmax FRC 335 (−0.3 SD) at 3 yrs and FEV1 0.61 L (58%) at 6 yrs. Occasional cultures of Haemophilus influenzae and Moraxella catarrhalis. Anti-S. aureus and P. aeruginosa: negative. F-elastase: normal. The patient has intermittent need of inhalation therapy. Conclusion: The clinical manifestations and the NPD result for mutation R117C are non classical. WS23.6 Ivacaftor treatment in patients with cystic fibrosis who have an R117H-CFTR mutation, the KONDUCT study R.B. Moss1, P.A. Flume2, J.S. Elborn3, J. Cooke4, S.M. Rowe5, S.A. McColley6, R.C. Rubenstein7, M. Higgins4, on behalf of the VX11–770-110 (KONDUCT) Study Group. 1Stanford University School of Medicine, Palo Alto, United States; 2Medical University of South Carolina, Charleston, United States; 3Queen’s University Belfast, Belfast, United Kingdom; 4Vertex Pharmaceuticals Incorporated, Boston, United States; 5University of Alabama at Birmingham, Birmingham, United States; 6Northwestern University Feinberg School of Medicine, Chicago, United States; 7The Children’s Hospital of Philadelphia, Philadelphia, United States

Longitudinal Study of Pulmonary Function in Infants With Postviral Chronic Pulmonary Disease

Adenovirus may cause severe injury of the lung parenchyma, characterized by bronchial epithelium necrosis, interstitial inflammation and alveolar damage, producing pathological alterations like bronchiolitis obliterans and a clinical course known as Postviral Chronical Pulmonary Disease (PCPD). Pulmonary function in these patients is characterized by a fixed and severe bronchial obstruction and alteration of the lung elastic recoll. The aim of this study was to characterize the evolution of pulmonary function in infants with PCPD. Pulmonary function tests were retrospectively analyzed in infants initially and after 6 to 34 months (mean 11.7 mo). A Sensormedics 2600 system was used. Tests were done in patients sedated with chloral hydrate. Compliance(Crs) and Resistance (Rrs) of the respiratory system obtained by the occlusion technique, and Maximal Flow at Functional Residual Capacity (VmaxFRC) obtained by the rapid thoracic-abdominal compression technique were analyzed. Vmax FRC was compared with the theoretical values by the Hanrahan's equation. Relation between Peak Tidal Expiratory Flow and Tidal Volume (PTEF/VT) from the Tidal Flow/Volume Curves were also considered. 12 patients (6 males and 6 females) were included. Mean age at first and second study were 14.5 (range 5 to 22), and 26.2 (range 11 to 54) months respectively. Mean time between both studies was 11.7 (range 6 to 34) months. Results:Table

Asthma and wheezing in the first six years of life. The Group Health Medical Associates.

Many young children wheeze during viral respiratory infections, but the pathogenesis of these episodes and their relation to the development of asthma later in life are not well understood. In a prospective study, we investigated the factors affecting wheezing before the age of three years and their relation to wheezing at six years of age. Of 1246 newborns in the Tucson, Arizona, area enrolled between May 1980 and October 1984, follow-up data at both three and six years of age was available for 826. For these children, assessments in infancy included measurement of cord-serum IgE levels (measured in 750 children), pulmonary-function testing before any lower respiratory illness had occurred (125), measurement of serum IgE levels at nine months of age (672), and questionnaires completed by the children's parents when the children were one year old (800). Assessments at six years of age included measurement of serum IgE levels (in 460), pulmonary-function testing (526), and skin allergy testing (629). At the age of six years, 425 children (51.5 percent) had never wheezed, 164 (19.9 percent) had had at least one lower respiratory illness with wheezing during the first three years of life but had no wheezing at six years of age, 124 (15.0 percent) had no wheezing before the age of three years but had wheezing at the age of six years, and 113 (13.7 percent) had wheezing both before three years of age and at six years of age. The children who had wheezing before three years of age but not at the age of six had diminished airway function (length-adjusted maximal expiratory flow at functional residual capacity [Vmax FRC]) both before the age of one year and at the age of six years, were more likely than the other children to have mothers who smoked but not mothers with asthma, and did not have elevated serum IgE levels or skin-test reactivity. Children who started wheezing in early life and continued to wheeze at the age of six were more likely than the children who never wheezed to have mothers with a history of asthma (P < 0.001), to have elevated serum IgE levels (P < 0.01), to have normal lung function in the first year of life, and to have elevated serum IgE levels (P < 0.001) and diminished values for VmaxFRC (P < 0.01) at six years of age. The majority of infants with wheezing have transient conditions associated with diminished airway function at birth and do not have increased risks of asthma or allergies later in life. In a substantial minority of infants, however, wheezing episodes are probably related to a predisposition to asthma.

Effects of CPAP on lung mechanics in infants with acquired tracheobronchomalacia.

Continuous positive airway pressure (CPAP) has been used in the treatment of infants with tracheobronchomalacia (TBM). However, the effects of CPAP on lung mechanics in these infants are unknown. We hypothesized that CPAP prevents airway collapse and improves forced exhalation. We studied respiratory mechanics of nine infants (age 15 +/- 3 mo, SEM) with acquired TBM documented by bronchoscopy, during quiet respiration and forced exhalation, using the esophageal balloon and rapid thoracic compression techniques, respectively. Measurements were made when infants received no CPAP and repeated when 5 and 8 cm H2O CPAP were applied to the airway opening via a modified Mapleson anesthesia circuit. Expiratory resistance (RL), midexpiratory tidal flow (VE50), and maximal flow at functional residual capacity (Vmax FRC) were compared at each level of CPAP. Vmax FRC increased threefold from baseline to 8 cm H2O CPAP (p < 0.005). In contrast, there was no difference in expiratory RL or in VE50 at any level of CPAP. These data suggest that in infants with acquired TBM, assessments of forced expiratory flow reflect the amount of CPAP necessary to prevent airway collapse during forced exhalation better than can measurements of tidal mechanics.

Longitudinal evaluation of pulmonary function in infants and very young children with cystic fibrosis

Thirty-two infants with cystic fibrosis (CF) had pulmonary function testing and chest radiographs at the time of diagnosis and on average 1 year later, when they had no acute respiratory symptoms. At diagnosis, 14 of 32 infants had respiratory symptoms (RESP) and 18 did not have respiratory symptoms (NRESP). There were no significant differences in age, weight, or length between the RESP and NRESP groups. At diagnosis, the RESP group had significantly lower forced expiratory flows compared to the NRESP group (41 +/- 32% vs. 98 +/- 48% predicted); however, there were no significant differences in functional residual capacity or chest radiographic scores. Between diagnosis and follow-up, the NRESP group had no significant change in pulmonary function but a decline in chest roentgenographic (CXR) scores (22 +/- 2 to 21 +/- 2). For infants in the RESP group, there were no significant changes in FRC or CXR score. Maximal expiratory flow at functional residual capacity (Vmax FRC) rose from diagnosis to 1 year follow-up (41 +/- 32% to 74 +/- 27% predicted; P < 0.002); however, at follow-up flows for the RESP group remained significantly lower than flows for the NRESP group (74% vs. 113% predicted; P < 0.0005). For the 32 infants with CF, there was significant correlation between percent predicted Vmax FRC at follow-up and at diagnosis (r = 0.47; P < 0.02). Those infants with lower percent predicted flows at diagnosis were more likely to have lower percent predicted flows 1 year later.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of Airway Responsiveness in Infants with Cystic Fibrosis

We compared the responses of cystic fibrosis (CF) (N = 14) and normal (N = 14) infants with inhaled methacholine. Airway function was assessed by forced expiratory flows at functional residual capacity (Vmax FRC) generated by the rapid compression technique, and methacholine responsiveness was quantitated as (1) TC: the threshold concentration to decrease Vmax FRC by 2 SD from baseline; (2) PC50: the provocative concentration to decrease Vmax FRC by 30%; and (3) SPC30; the slope of the dose-response curve between TC and PC30. There were no significant differences in age between CF and normal infants (16 +/- 8 versus 17 +/- 5 months, p greater than 0.3); however, the CF infants were shorter (74 +/- 10 versus 81 +/- 5 cm, p less than 0.05), had lower absolute Vmax FRC (241 +/- 103 versus 374 +/- 113 ml/s, p less than 0.001), and tended to have lower percentage of predicted flow values (87 +/- 13 versus 111 +/- 34%, p less than 0.10). Comparison of the indices of airway responsiveness revealed no difference in logTC; however, the CF infants had smaller, more negative values for logPC30 (-0.76 +/- 0.52 versus -0.22 +/- 0.53, p less than 0.02) and steeper slopes to their dose-response curves (logSPC30, 2.42 +/- 0.45 versus 1.88 +/- 0.74, p less than 0.025). Indices of airway responsiveness correlated significantly with baseline Vmax FRC (% of predicted). After the influence of baseline flow upon airway responsiveness was accounted for by multiple linear regression analysis, there was a tendency for CF infants to be more responsive than control infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Short-term variability of pulmonary function tests in infants with bronchopulmonary dysplasia.

We determined the short-term variability of pulmonary function in infants recovering from bronchopulmonary dysplasia. Sixteen infants with birth weight of 1,231 +/- 929 grams (mean +/- SD) and gestational age of 29 +/- 4 weeks were studied twice at 17 +/- 8 weeks postnatally at intervals of 4 to 8 days during a period of clinical stability. The infants were still on supplemental oxygen but were off diuretics and bronchodilators. We used a modification of the rapid thoracic compression method to measure forced expiratory flow (Vmax FRC) and the time constant (tau) of expiratory flow at functional residual capacity. Thoracic gas volume (TGV), mean and total airway resistance (RawM and RawT), and mean and total specific airway conductance (SGawM and SGawT) were measured in a whole body pressure plethysmograph. An esophageal balloon was used to measure dynamic pulmonary compliance (Cdyn). Variabilities were defined as the standard deviation of percent changes between the first and second tests. They were 30% for VmaxFRC, 23% for tau, 12% for TGV, 20% for RawM, 35% for RawT, 25% for SGawM, 72% for SGawT, and 23% for Cdyn. All these tests are useful in assessing pulmonary function of infants with BPD; however, their variability must be taken into account when interpreting short-term changes.

Ipratropium bromide and airways function in wheezy infants.

The airway response to nebulised ipratropium bromide was studied in 17 chronically or recurrently wheezy infants aged 4-15 months. The peripheral airway response was assessed by the change in maximum flow at functional residual capacity (Vmax FRC) and the upper and central airway response by the change in specific airways resistance. The significant reduction in specific airways resistance after treatment with ipratropium bromide signified an improvement in central and upper airway function. No change was found, however, in Vmax FRC and hence in peripheral airway function. It seems that, as in older subjects, inhaled antimuscarinic, anticholinergic drugs have their maximum effect on the large airways, and this may explain their lack of effect in the management of acute bronchiolitis.

EFFECTS OF PRENTAL SMOKING ON LUNG FUNCTION IN INFANTS UNDER 4 MOTH OF AGE

Exposure to parental smoking has been associated with decreased lung function and respiratory symptoms in later life. Animals exposed to cigarette smoke have been reported to have altered lung volume compared to controls. We selected 87 infants <4 mo who were randomly enrolled in a prospective study of risk factors for lung disease. Maximal flows at FRC (Vmax FRC) were measured by the rapid chest compression technique, and FRC by helium-dilution. 20 infants' mothers smoked during the pregnancy (S) and 67 did not (NS). There were significantly (<.001) more smoking fathers in the S group. The prevalence of chronic respiratory problems in the family was the same in the both groups. Results are summarized in the table: These preliminary data suggest that infants born to smoking mothers show a tendency to have a larger lung parenchyma and lower volume-corrected flows. We speculate that dysnaptic growth patterns may occur in-utero, and are consistent with decreased flows, but larger lung volumes are observed in older children raised by smoking parents.