Partial Expiratory Flow-volume Research Articles

Fetal Origins of Asthma: A Longitudinal Study From Birth to Age 36 Years

To determine the relationship between the low percentage of expiratory time necessary to reach tidal expiratory flow (tPTEF/tE) and flow at the end tidal point (VmaxFRC) in early infancy to the development of asthma, airflow limitation, and airway structural abnormalities in this 36-year birth cohort of the Tucson Children’s Respiratory Study.This is a birth cohort consisting of 1246 healthy infants born between 1980 to 1984 enrolled in the TCRS. Only 180 infants <6 months of age were tested by using the chest compression technique for pulmonary function testing because this technique was not developed until the end of the enrollment period.Demographic information was obtained via parent completed questionnaires. Infant lung function testing included tidal breathing indices, functional residual capacity via a helium-dilutions-gas-equilibration method, and partial expiratory-flow curves, from which the tPTEF/tE was determined. VmaxFRC was determined via partial expiratory flow-volume curves by using the chest compression technique. Active asthma was defined as a physician diagnosis of asthma at any age, with active symptoms within the previous year based on questionnaires obtained every 2 to 4 years between the ages of 6 and 36 years. Survey information, spirometry (prebronchodilator and postbronchodilator and full lung volumes), and high-resolution computed tomography of the chest was completed at the age of 26 years. Data were analyzed via multivariate linear regression models and generalized estimating equations.A total of 180 infants, who underwent pulmonary function testing, were compared with 1066 participants who did not undergo testing. The tested cohort revealed 8% with active asthma at the age of 6 years and 18% at the age of 36 years. Levels of infant tPTEF/tE and VmaxFRC were lower for participants who developed active asthma. tPTEF/tE and VmaxFRC were associated with a significant risk for active asthma (P = .003 and P =.007, respectively) and those in the lowest tertile of both indices were at highest risk (P = .009 and P = .01, respectively). Both tPTEF/tE and VmaxFRC were associated with an increased odds of developing active asthma between the ages of 6 and 36 years (70% [P = .001] and 55% [P = .005], respectively). At the age of 26 years, low infant tPTEF/tE was associated with reductions in airway diameter, total area, and luminal and wall areas, whereas VmaxFRC was associated with reduced forced expiratory volume in 1 second to forced vital capacity, forced expiratory volume in 1 second, and forced expiratory flow 25% to 75% levels.Reduced tPTEF/tE and VmaxFRC levels in infancy may indicate an increased risk for active asthma by the age of 36 years on the basis of pulmonary function testing and airway imaging in adulthood.Recognizing risk factors for asthma may extend beyond family history and personal history of atopy and respiratory infections. This study reveals that airflow limitation early in infancy may help predict asthma later in life and warrants further studies to standardize methods for clinical use and application. Understanding the time course of asthma development is essential in prevention and treatment.

Classification of voluntary cough airflow patterns for prediction of abnormal spirometry.

Measurement of partial expiratory flow-volume curves has become an important technique in diagnosing lung disease, particularly in children and in the elderly. The objective of this study was to investigate the feasibility of predicting abnormal spirometry using the partial flow-volume curve generated during a voluntary cough. Here, abnormal spirometry is defined as less than the lower limit of normal (LLN) predicted by standard reference equations [1]. Cough airflow signals of 107 subjects (56 male, 51 female) were previously collected [2] from patients performing spirometry in a pulmonary function clinic. A variety of features were extracted from the airflow signal. A support vector machine (SVM) classifier was developed to predict abnormal spirometry. Airflow signal features and SVM parameters were selected using a genetic algorithm. The ability of the classifier to distinguish between normal and abnormal spirometry based on cough flow was evaluated by comparing the classifiers decisions with the LLN for the given subject's spirometry, including forced expiratory volume in one second (FEV1), forced vital capacity (FV C), and their ratio (FEV1=FV C%). Findings indicated that it was possible to classify patients whose spirometry results were less than the LLN with an overall accuracy of 76% for FEV1, 65% for FV C, and 76% for the ratio FEV1=FV C%. Accuracies were determined by repeated double cross-validation [3]. This study demonstrates the potential of using airflow measured during voluntary coughing to identify test subjects with abnormal spirometry.

Reversibility of the Pulmonary Function Based on the Partial Flow-volume Curve Predicts the Efficacy of Bronchodilator Therapy for Treating Chronic Cough

Partial expiratory flow-volume curves have the potential to detect mild bronchoconstriction because they are not affected by the modulatory effects of deep inspiration. The aim of this study was to investigate the relationship between the efficacy of bronchodilator therapy (BDT) in treating the cough and to assess the increase in the expiratory flow of the partial flow-volume curve at 40% above the residual volume level (PEF40) caused by treatment with a short-acting beta-2 agonist (SABA) in patients with chronic nonproductive cough. We measured the reversibility of PEF40 caused by a SABA in 42 patients with chronic nonproductive cough at visit 1 (day 0). The patients received BDT for six days. The visual analogue scale (VAS) was used to assess the efficacy of BDT in treating coughing at visit 2 (day 7) (0 mm, 'no cough;' 100 mm, 'no change in coughing'). Reversibility of the PEF40 was correlated (r=0.690, p<0.001) with the VAS score determined at visit 2 and was higher in the patients with cough variant asthma (CVA) (44.9 ± 18.3%) than in those with atopic cough (13.4 ± 10.4%) (p<0.01). Reversibility of the PEF40 predicted the efficacy of BDT in patients with chronic nonproductive cough and helped to identify patients with CVA.

Relation between partial and raised volume forced expiratory flows in sick infants

The maximal expiratory flow-volume (MEFV) and the partial expiratory flow-volume (PEFV) maneuvers are interchangeably performed when testing infant lung function. In recent years, the MEFV has gained popularity over the PEFV as it offers the investigator various forced expiratory flow and volume variables in addition to the sole, maximal flow at functional residual capacity (Vmax FRC) available from the PEFV maneuver. Both types of measure are considered to provide information on airway function. To compare Vmax FRC values by PEFV to flows at low lung volumes by MEFV in infants suffering from a variety of illnesses. Retrospective analysis of records of 175 infants attending a tertiary out-patient clinic (age range 2-234 weeks). Comparisons between parameters derived from the PEFV and MEFV curves were made by linear regression and by Bland-Altman plots. Vmax FRC highly correlated with forced expiratory flows at 85% of forced vital capacity (FEF85; r = 0.87, P < 0.0001) with a mean bias of 20 ml/sec, and at 75% (FEF75; r = 0.83, P < 0.0001) with a greater mean bias of -72 ml/sec, but less with forced expired volume in 0.5 sec (FEV0.5; r = 0.66, P < 0.0001) showing a much wider scatter especially in infants with more severe obstruction. Same agreement between Vmax FRC and FEF85 or FEF75 was seen when presented as z-scores (r = 0.77 and 0.76; respectively). Regardless of the maneuver performed, PEFV or MEFV, Vmax FRC and FEF85, and FEF75 show high agreement in sick infants. As they both describe small airways function, both maneuvers may be interchangeable.

Airway Responses to the Inhalation of Cotton Dust and Cotton Bract Extracts

Background: Exposure to dust in the cotton industry is associated with respiratory dysfunction. Healthy subjects challenged with cotton bract extract (CBE) develop transient airway hyperresponsiveness. CBE, a major component of cotton dust, is potentially an important agent for studying byssinosis. Objectives: To compare airway responses to cotton dust extract (CDE) and CBE in healthy subjects. Methods: In 21 healthy, non-smoking subjects we compared the effects of CBE and CDE in a double-blind random order, following a 10-min aerosol inhalation. The response to methacholine (MCh) 2 h following CBE or CDE was measured. Lung function was recorded using maximal (MEFV) and partial expiratory flow volume (PEFV) curves, measuring MEF at 60% of baseline vital capacity below total lung capacity [MEF_40%(P)] on the PEFV curve. Responders were subjects who developed a 20% or greater fall in MEF_40%(P) following extract challenge. Endotoxin levels were low for CBE (5.71 EU/mg) and CDE (31.88 EU/mg). Results: There were 18 responders to CBE and 17 responders to CDE.The average maximal falls in MEF_40%(P) were 70 ± 4.9 and 70 ± 4.4% of baseline (nonsignificant) following CBE and CDE, respectively. All subjects enhanced their MCh response following CBE or CDE. The MCh dose which reduced MEF_40%(P) by 40% was identical for CBE and CDE (1.3 µg/ml). Conclusions: We conclude that CBE and CDE exert similar physiologic effects.

Effect of deep inspiration on airway caliber in children with asthma.

The objective of this study was to assess the effect of deep inspiration (DI) on airway caliber in school-age children with asthma. Thirty children with asthma (10 from each group of mild, moderate, and severe persistent asthma as defined by the National Asthma Education and Prevention Program guidelines of the National Heart, Lung, and Blood Institute) were enrolled, and their results were compared to those obtained in 7 healthy children. Subjects performed a partial expiratory flow volume curve (P) initiated from approximately 70% of vital capacity (VC) followed by a maximal expiratory flow volume (M) maneuver begun from total lung capacity (TLC). The M/P ratio at 30% of the VC (M/P30) was calculated. Specific airway conductance (sGaw) was measured before and immediately after DI, using standard techniques. Differences in M/P30 and sGaw ratios between asthma and control groups were compared with Student's unpaired t-tests. One-way ANOVA was used to compare the effect of DI on M/P30 and sGaw ratios among the various asthma severity groups. The M/P30 ratio (mean +/- 1 SD) was significantly lower in children with moderate and severe persistent asthma (0.73 +/- 0.21 and 0.72 +/- 0.1, respectively) than in healthy controls (1.69 +/- 0.62) (P < 0.05). In mild persistent asthmatics, there was limited bronchodilation (M/P30 = 1.1 +/- 0.35, P = 0.052). There was a significant inverse correlation between M/P30 ratio and severity of asthma (r = -0.684, P < 0.01). The mean sGaw ratio was decreased in asthmatic subjects compared to healthy controls (0.98 +/- 0.17 vs. 1.13 +/- 0.16, P = 0.062). In conclusion, in school-age children, the effects of DI on airway caliber are similar in direction to those observed in adults, i.e., bronchodilation in healthy and mild asthmatics, and bronchoconstriction (BC) in moderate to severe asthmatics. This finding suggests that forces that determine airway caliber in school-age children are similar to those forces in adults.

Clinical Assessment of Airway Function in Health and Disease

After completing this article, readers should be able to: 1. Describe which pulmonary function tests can be used to measure tidal lung mechanics and forces of expiratory flow. 2. Describe the airway conditions that can be assessed radiographically. 3. Delineate clinical methods of diagnosing central airway collapse and quantifying airway wall stiffness. Clinical assessment of pulmonary function is a valuable tool in the identification and treatment of neonatal disease. As shown in the Table⇓, a multitude of tests is available to identify and measure airway function clinically in pediatric populations. These tests often identify functional abnormalities in the airways of preterm infants exposed to mechanical ventilation, including elevated resistance, decreased forced expiratory flow, airway hyperreactivity, and excessive central airway collapsibility. In addition to aiding in diagnosis, these procedures help predict the effects of early injury on future airway growth and function and can be used to evaluate the effectiveness of newer therapies. Serial evaluation of airway function is especially useful for infants who fail to improve as expected; who have frequent severe exacerbations of pulmonary dysfunction; or who demonstrate stridor, chronic wheezing, or focal areas of chronic atelectasis or hyperinflation. View this table: Table Clinical Evaluation of Airway Function With the simultaneous measurement of respiratory pressures, volumes, and air flow, pulmonary mechanics can be monitored relatively noninvasively. Pulmonary function profiles can be determined to assess initial disease etiology, the response to therapy, and disease sequelae during follow-up. For example, the pressure-volume relationship of a preterm infant can identify the degree of respiratory function and monitor the response following surfactant administration (Fig. 1). The evaluation of tidal breath pressure-volume relationships serves as a tool to optimize the parameters of mechanical ventilation (Fig. 2). Over time, sequential pulmonary mechanics can be used to monitor the progression and improvement in both lung and airway abnormalities (Fig. 3). Dynamic …

Association of tobacco smoke exposure and respiratory syncitial virus infection with airways reactivity in early childhood.

Exposure to infectious agents and environmental tobacco smoke are thought to induce bronchial hyperresponsiveness (BHR). This study was undertaken to determine the effects of passive exposure to tobacco smoke and respiratory syncitial virus (RSV) lower respiratory infection (LRI) during infancy on the occurrence of BHR in the first 2 years of life. Eighty-six cases of documented RSV (mean age, 188 days) and 78 controls (mean age, 162 days) were enrolled from the clinic and in-patient service of a single hospital. None had a history of prior LRI. Subjects were studied at 6-month intervals up to 19 months of age with a standardized respiratory illness and parental smoking questionnaire, partial expiratory flow-volume curves by the "hug" (rapid thoracic compression) technique, and methacholine challenge. Exposure to maternal and paternal cigarette smoking, maternal history of asthma, and mold exposure were associated with decreased levels of length-corrected maximal flow at functional residual capacity (V'(maxFRC)). RSV-LRI was not related to V'(maxFRC). After adjustment of V'(maxFRC) for these factors, V'(maxFRC) was a significantly and positively correlated with a methacholine concentration provoking a 40% fall in V'(maxFRC) (PC40) and negatively correlated with dose-response slope. After adjustment for V'(maxFRC), there were no independent effects of tobacco smoke exposure or RSV-LRI on methacholine responses. These data do not support a role for RSV as a risk factor for airways reactivity in childhood and indicate that exposure to tobacco smoke affects airways reactivity through its effects on airways.

Maximal and partial expiratory flow rates in a population sample of 10- to 11-yr-old schoolchildren. Effect of volume history and relation to asthma and maternal smoking.

The effect of volume history on forced expiratory flow rates has been reported to differ between patients with asthma and healthy persons, and it has been hypothesized that the peripheral airway inflammation of patients with asthma may underlie this difference. There are no published data, however, on the distribution of such volume history effects or the relation of these effects to airways disease in children. We obtained combined partial and maximal forced expiratory flow-volume curves on 1,834 children, age 10-11 yr, in eight communities in the United States and Canada. The effect of a deep inhalation on forced expiratory flow rates at low lung volumes was quantitated by the ratio of V (30) during a maximal expiratory maneuver (V (30M)) to V (30) during a partial expiratory maneuver (V (30P)). The V (30M)/V (30P) ratio was slightly higher among girls than boys (1.26 versus 1.18, p = 0.0001) indicating that a deep inhalation increased V (30) slightly more among girls than among boys. The V (30M)/V (30P) ratio was related to neither history of asthma nor to maternal smoking. In contrast, most spirometric indices from either the maximal or the partial expiratory flow-volume curve were lower in association with a history of asthma or a report of maternal smoking. The ratio of FEF(25-75)/FVC was particularly consistent as a measurement that discriminated both of these effects in boys and girls. These results suggest that the measurement of volume history effects offers no benefits for epidemiological studies of childhood respiratory disease whereas spirometric indices such as the FEF(25-75)/FVC ratio are quite sensitive to the effects of asthma and environmental tobacco smoke exposure on the airways.

Influence of ethnicity and gender on airway function in preterm infants.

While maximal expiratory flow at functional residual capacity, calculated from partial expiratory flow volume curves (V'maxFRC), is a valuable measure of peripheral airway function in infants, limited data are available in preterm infants despite their high prevalence of respiratory problems. To investigate the influence of gender and ethnic group, V'maxFRC and other indices of respiratory function were measured in 28 black and 28 white preterm infants (50% female in each group) at time of discharge from the neonatal unit (mean [SD] weight 2.36 [0.3] kg, postnatal age 19 [9] d). No infant had any history of cardiorespiratory disease and all were born to non-smoking mothers. V'maxFRC tended to be higher in girls than boys (115 versus 94 ml.s-1 [95% CI: -5; 47]) but there was no significant difference in this parameter between black and white infants (111 versus 98 ml.s-1 [95% CI of difference: -12; 40]). Respiratory resistance (Rrs) was significantly lower in black than white infants (95% CI: -2.9; -0.4 kPa.L-1.s) and tended to be lower in female than male infants (95% CI: -2.3; 0.2 kPa.L-1.s). Similarly, time to peak tidal expiratory flow as a proportion of total expiratory time (tPTEF:tE) was significantly longer in black than white (95% CI: 0.06, 0.20) and in female than male (95% CI: 0.02, 0.15) infants. These findings suggest that certain parameters of airway function may be influenced by both ethnic group and gender in preterm infants, both of which should therefore be taken mw account when investigating the effects of disease and/or therapeutic interventions in this group.

Lung function in infants with sickle cell disease.

We performed pulmonary function testing in 20 infants (11 male and 9 female; ages 3-30 months) with sickle cell disease to assess whether abnormal lung function develops early in life. Respiratory system compliance (Crs) and resistance (Rrs) were measured by the passive occlusion technique, functional residual capacity (FRC) was measured by the nitrogen washout technique, and tidal flow-volume loops and partial expiratory flow-volume curves were obtained by the thoracoabdominal compression technique to detect airway obstruction. Patients with Hb SS (Group I, n = 12) had significantly lower hemoglobin levels and a higher (but not significant) incidence of acute chest syndrome (ACS), vasoocclusive crisis (VOC), splenic sequestration, transfusions, and history of intermittent bronchospasm compared to with patients with hemoglobinopathies Hb SC, Hb Sbt and Hb SF (Group II; n = 8). Both groups had elevated FRC, decreased maximum expiratory flows at FRC (V'max,FRC), and decreased time needed to reach peak expiratory flow (tme/tE), suggesting lower airway obstruction (LAO) and hyperinflation. Restrictive disease was found in only three patients of Group I. Our findings suggest that in sickle cell disease (especially among patients with Hb SS), abnormal lung function (predominantly LAO) may be present in early infancy. Airway reactivity may play a role in the pathogenesis, but the relation to VOC or ACS remains unclear.

The Effect of Regular Salbutamol on Lung Function and Bronchial Hyperresponsiveness in Normal Subjects and Nonasthmatic Atopic Subjects With Allergic Rhinitis

The effects of regular inhaled beta-agonist treatment on lung function remain a controversial issue. In an earlier study, the administration of regular inhaled salbutamol resulted in negative changes in FEV1 not only in asthmatics, but also in nonasthmatic atopic subjects. The aim of this study was to confirm these findings and also to examine whether regular inhaled salbutamol would increase bronchial hyperresponsiveness in atopic or normal individuals. The study was a randomized, double-blind, placebo-controlled, crossover investigation. There were two groups: 10 normal healthy subjects (group A) and nine nonasthmatic atopic subjects (group B). Subjects received inhaled salbutamol or identical placebo for periods of 6 weeks, the dose being increased in stepwise fashion at 2-week intervals. Changes in lung function were assessed by measuring spirometric values, airways conductance, and changes in complete and partial expiratory flow volume curves. Changes in these parameters following a methacholine challenge were used to assess bronchial hyperresponsiveness. No statistically significant differences in lung function or bronchial hyperresponsiveness were noted to occur as the result of treatment in either group. Our results do not support the view that regular inhaled salbutamol in normal or atopic subjects without asthma causes adverse changes in the airways.

Shape and position of the complete dose-response curve for inhaled methacholine in normal subjects.

Plateaus on the inhalation concentration-response curve have been described in normal subjects and patients with mild asthma. To determine the prevalence of plateaus on inhalation concentration-response curves, and the position of the curves in normal subjects, we measured complete dose-response curves for methacholine (1 mg/ml to 256 mg/ml) in 73 nonatopic, nonsmoking, nonasthmatic normal subjects between the ages of 20 and 76 yr. Measurements included FEV1, maximal expiratory flow at 50% and 30% of vital capacity on partial and complete forced expiratory flow-volume curves (Vmax50p, Vmax50c, Vmax30p, Vmax30c) and pulmonary resistance (RL). Plateau responses, EC50 values and slopes were measured. Plateaus were present in 25, 27, 24, 34, 35, and 16 subjects for FEV1, Vmax50c, Vmax30c, Vmax50p, Vmax30p, and RL, respectively. In those who achieved a plateau, the mean maximal decrease in FEV1 (+/- SD) was 21 +/- 8%, in Vmax50c it was 46 +/- 16%, in Vmax50p it was 67 +/- 12%, in Vmax30c it was 58 +/- 21%, and in Vmax30p it was 75 +/- 15%, and the increase in RL was 213 +/- 89%. In summary, the results of this study showed that easily identifiable plateaus develop on the inhalation concentration-response curves of approximately 40% of normal subjects after only moderate decreases in maximum flow and increases in RL. Maximal response at the plateau was greater on partial flow-volume curves and at lower lung volumes (30% versus 50% of VC). Comparison of these data with data from patients at risk for airway hyperresponsiveness will allow definition of the mechanisms leading to airway hyperresponsiveness.

Tracheobronchial Constriction in Asthmatics Induced by Isocapnic Hyperventilation With Dry Cold Air

Although it is well known that isocapnic hyperventilation (IHV) with dry cold air produces airway constriction in asthmatic subjects, the site of airway narrowing is nuclear. To address this issue, we have quantified the tracheal and bronchial response to IHV with dry cold air in 15 patients with mild asthma and 7 healthy control subjects. We employed the acoustic reflection technique to evaluate changes in airway cross-sectional areas caused by IHV with dry cold air. Airway areas were measured during tidal breathing before and 5 to 10, 30, 60, and 90 min following cold air challenge. For analysis purposes, airway areas were divided into three anatomic segments: extrathoracic tracheal segment, intrathoracic tracheal segment, and main bronchial segment. These segments were assessed at a fixed volume below total lung capacity. Maximal and partial expiratory flow-volume curves were also obtained before each set of area measurements. In normal subjects, IHV with dry cold air caused no significant changes in FEV1, flow at 30% of the vital capacity in the partial curve (V30p), or airway areas. In asthmatics, at 5 to 10 min after challenge, we found that FEV1 decreased by 22 +/- 5% (mean +/- SEM) (p < 0.0001), V30p by 33 +/- 8% (p < 0.003), intrathoracic tracheal area by 10.7% +/- 2% (p < 0.03), and main bronchial area by 14 +/- 3% (p < 0.003). At 30 min, tracheal and main bronchial areas were returned to baseline levels; however, FEV1 and V30p were still significantly decreased, by 13 +/- 3% and 16 +/- 4%, respectively. We conclude that in asthmatics, IHV with dry cold air causes both tracheal and bronchial constriction, and that recovery seems to occur first in the central airways.

Relationship between an index of tidal flow and lower respiratory illness in the first year of life.

The ratio of time to tidal peak flow (Tme) to total tidal expiratory time (Te) has been reported to be decreased in infants who later develop wheezing lower respiratory tract illness (LRI) in the first year of life. The relationship between Tme/Te to the subsequent occurrence of LRI was studied in 98 infants in whom the first measurement of pulmonary function (PFT) was made before the age of 6 months and before the occurrence of any LRI. Occurrence of LRI was evaluated by standardized questionnaires at well-baby visits, through biweekly telephone calls to mothers, and review of all visits to physicians. Tme/Te was derived from 10 tidal breathing loops during stable respiration. Partial expiratory flow-volume curves were obtained with the rapid compression technique, and passive respiratory mechanics were evaluated by the single breath occlusion technique. Analysis of Tme/Te was stratified by age (< or = 10 weeks, > 10 weeks to 6 months) to take into account the age-related decline in Tme/Te. Among 80 infants first tested at < or = 10 weeks, Tme/Te was 12.4% shorter in those who developed a LRI vs. those who did not (P = 0.46); for 18 infants tested after 10 weeks, the difference was 1.9% (P = 0.39). Among male infants, the decrease in Tme/Te was observed only for those studied at < or = 10 weeks (16%, P = 0.16). For females, decreases were observed for those tested at < or = 10 weeks (11%, P = 0.83) and those tested after 10 weeks (17.5%, P = 0.09). Poisson regression analysis which included data for multiple measurements of Tme/Te over the first year of life and adjusted for age-at-test and maternal smoking during pregnancy also demonstrated a greater decrease in Tme/Te in female infants who subsequently develop an LRI (P = 0.08). Level of Tme/Te was not consistently related to level of respiratory system resistance (RRS) or flow at functional residual capacity (VFRC). Level of VFRC has been shown previously to be related to the occurrence of LRI and in this study to RRS(P = 0.007). The results indicate (1) a shortened Tme/Te is only weakly associated with the development of LRI in the first year of life; (2) this ratio is a less precise and an epidemiologically less useful measure than is VFRC to investigate groups of infants with and without LRI and without clinically significant underlying lung disease.

Maternal smoking during pregnancy. Effects on lung function during the first 18 months of life.

The present investigation evaluated the effects of maternal smoking during pregnancy on the growth of lung function during the first 18 mo of life in 159 infants who were part of a longitudinal study of the effects of maternal smoking on respiratory health. Infant pulmonary function was assessed at 2 to 6 wk of age and at 4 to 6, 9 to 12, and 15 to 18 mo of age by partial expiratory flow-volume curves and helium dilution FRC. Maternal smoking was assessed by standard questionnaire and urine cotinine measurements. Maternal smoking during pregnancy was associated with a reduction of 9.4 +/- 4.3 ml (p = 0.029) for FRC and 33 +/- 12.3 ml/s (p = 0.008) reduction for flow at FRC (VFRC) after controlling for the effects of growth (length). The effect of maternal smoking was greater for female infants than for male infants. At 1 yr female infants exposed in utero were predicted to have a 16% reduction in VFRC compared with 5% for male infants. No sex difference was seen for FRC or VFRC/FRC. Exposure to environmental tobacco smoke in the postnatal period was not significantly related to reduced FRC or VFRC. These data provide further evidence that maternal smoking during pregnancy may play a greater role than postnatal and childhood exposure on the observed effects on lung function in children.

The severity of breathlessness during challenges with inhaled methacholine and hypertonic saline in atopic asthmatic subjects. The relationship with deep breath-induced bronchodilation.

The severity of breathlessness at given degrees of airway obstruction varies between patients with asthma. It has been postulated that the symptoms during bronchoconstriction are determined in part by involvement of airway inflammation. We compared the severity of breathlessness at various degrees of acute airway obstruction between a direct stimulus of airway smooth muscle, methacholine, and an indirectly acting stimulus, hypertonic saline. Twelve atopic asthmatic adults (mean +/- SD; age 25.3 +/- 3.4 yr; baseline FEV1 91.2 +/- 10.4% pred; PC20 1.0 mg/ml methacholine +/- 1.7 doubling dose) entered a methacholine and a hypertonic saline period in random order. In each period doubling doses of either methacholine (0.03 to 256 mg/ml) or hypertonic saline (0.9 to 14.4% NaCl) were inhaled on two occasions 7 d apart, using standardized tidal breathing methods. The response was obtained by FEV1 and, in order to assess volume history effects on airway caliber, by the ratio of flows obtained from volume history standardized maximal and partial expiratory flow-volume curves (M/P ratio). Breathlessness was measured by a visual analogue scale (VAS), which ranged from 0 (none) to 100% (most severe experienced). The subjects were blinded to the response in lung function. The changes from baseline in VAS scores at intervals of 5% fall in FEV1 (delta VAS) and the changes in M/P ratios (delta M/P ratio) were calculated by linear interpolation. The results were analyzed by MANOVA. There were no differences in baseline FEV1 or baseline VAS scores between the methacholine and hypertonic saline periods (p > 0.40).(ABSTRACT TRUNCATED AT 250 WORDS)

90 STANDARDISATION OF THE HERING-BREUER DEFLATIONARY REFLEX

We have recently reported that the forced partial expiratory flow volume technique induces the Hering-Breuer deflationary reflex in infants. The factors responsible for initiating this reflex in man have never been documented. We investigated the effects of altering the peak and rate of rise of jacket pressure and of inflating the jacket at different times in the respiratory cycle on the strength of the reflex. Reflex strength was determined by the rate of fall of oesophageal pressure post jacket inflation. 28 healthy newborn infants were studied using a “Hammersmith” jacket and pneumotachograph/reverse plethysmograph system. There was a significant relationship between peak oesophageal pressure, reduction in oesophageal pressure post inflation, rate of inflation of jacket and the reflex strength (p<0.001). However, there was no relationship between the position in the respiratory cycle of jacket inflation and reflex strength. The reflex was most reproducible, occurring 0.12-0.16 seconds after onset of inflation, when the jacket inflation pressure was at least 30cms H2O, the rate of rise of the jacket was less than 0.2 seconds and inflation commenced around end inspiration. We recommend that these conditions are used to standardise the Hering-Breuer deflationary reflex.

Factors determining lobar emptying during maximal and partial forced deflations in nonhomogeneous airway obstruction in dogs.

The partial expiratory flow-volume (PEFV) maneuver has been proposed as a sensitive test to detect nonuniform airway disease. We tested this hypothesis in seven dogs in an open-chest preparation in which the right upper lobe (RUL) bronchus was partially obstructed. Alveolar capsules were placed on the obstructed RUL and nonobstructed right lower lobe (RLL) to measure respective alveolar pressures (Palv) during PEFV and maximal expiratory flow-volume (MEFV) maneuvers. PEFV curves were initiated at about 75% of the whole-lung vital capacity (VC). A Pitot static tube was placed into the airway to identify sites of flow limitation (choke-points [CP]), frictional pressure losses to CP (Pfr), CP area (A*), and compliance (K*). Results were analyzed at 45% VC, where a central tracheal CP was identified, and at 29% VC, where lobar CP were identified. At both lung volumes, the results showed that during PEFV, Palv and flows of the obstructed RUL decreased, whereas Palv and flows of the RLL increased compared with values obtained during MEFV. However, total maximal expiratory flow (Vmax) did not change between maneuvers. At 45% VC, although Pfr decreased during PEFV, this decrease was not large enough to result in an increase in A* and hence total Vmax because CP were identified in the noncompliant trachea. At 29% VC, offsetting changes in lobar A* and flow occurred between maneuvers: during PEFV, RLL A* and flow relatively increased while RUL A* and flow decreased. This study describes the mechanisms that explain why the PEFV maneuver is not useful in the detection of nonhomogeneous airway obstruction.

Effect of an inhaled neutral endopeptidase inhibitor, thiorphan, on airway responsiveness to leukotriene D4 in normal and asthmatic subjects

Cysteinyl leukotrienes are potent inflammatory mediators that are considered to play a role in the pathophysiology of asthma. It can be postulated that leukotrienes exert their bronchoconstricting effects, in part, through secondary release of endogenous neuropeptides. We examined the effect of inhaled thiorphan, an inhibitor of a neuropeptide degrading enzyme, on the concentration-response curve to leukotriene D4 (LTD4) in a two-period, double-blind, cross-over and placebo-controlled study, in 16 nonasthmatic and 12 asthmatic subjects. Thiorphan or placebo were aerosolized and administered in two 0.5 ml doses of 1.25 mg.ml-1 each, 10 min prior to LTD4 inhalation. The airway response was measured by forced expiratory volume in one second (FEV1) and partial expiratory flow-volume curves (expiratory flow at 40% of forced vital capacity; V40p), and expressed as % fall from baseline. Complete concentration-response curves to inhaled LTD4 were recorded and characterized by their position (provocative concentration producing a 20% fall in FEV1 and a 40% fall in V40p; PC20FEV1 and PC40 V40p) and, in the nonasthmatics, also by the maximal-response plateau (MFEV1, MV40p). Post-pretreatment baseline values of FEV1 and V40p were not different between thiorphan and placebo pretreatment. In both groups of subjects, there was no significant difference in lnPC40V40p or lnPC20FEV1 to LTD4 between the two pretreatments mean difference +/- SD (in doubling concentrations): 0.12 +/- 0.73 and -0.19 +/- 1.23, respectively, in asthmatics; and 0.17 +/- 0.95 and -0.99 +/- 1.95, respectively, in nonasthmatics. The maximal-response plateau could not be obtained in the majority of the asthmatic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)