INTRODUCTION

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Forced expiratory flow rates at low lung volumes often differ between maximal (i.e., initiated from total lung capacity) and partial (i.e., initiated from below total lung capacity) forced expiratory manuevers because of the effects of a deep inhalation on expiratory flow-volume relationships. On average, healthy adults display slightly higher forced expiratory flow at a specified lung volume during a maximal expiratory maneuver than during a partial expiratory maneuver (1). Patients with asthma display a more variable response to a deep inhalation, in some cases exhibiting lower forced expiratory flow during a maximal maneuver than during a partial maneuver. Lim and coworkers (4) hypothesized that peripheral airway inflammation underlies the altered volume history effect that may be seen in adult patients with asthma, and Pliss and coworkers (5) were able to establish that such a relationship exists based on peripherally lavaged mediator and cellular indices.

We wished to assess the potential utility of volume history effects in studying children with asthma or possible airway inflammatory stimuli. Indices derived from maximal and partial forced expiratory maneuvers were examined in relation to reported history of asthma and maternal smoking status, two factors with adverse effects on pulmonary function that may be related to peripheral airway inflammation.

	METHODS

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Population

In 1988, a study of the effects of air pollution on respiratory symptoms and lung function among all fourth- and fifth-grade children enrolled in the public and parochial schools in 24 U.S. and Canadian communities was initiated (6, 7). During the first year of the study, the fifth-grade children in eight communities were asked to perform combined maximal and partial flow-volume maneuvers, as described below. A total of 2,043 children performed the maneuver in the eight communities. The study protocol was approved by the institutional review board of the Brigham and Women's Hospital, Boston, MA. Written informed consent was obtained from parents prior to participation.

Flow-Volume Maneuvers

Combined partial and maximal forced expiratory flow-volume maneuvers were performed using a dry rolling-seal spirometer (Spiroflow; P.K. Morgan Instruments Inc., Andover, MA) interfaced with a PC through an A-to-D board. A computer program developed by the manufacturer to meet the specifications of the investigators was used to read and store the data sent to the PC from the spirometer. Children were given brief instructions before the combined maneuvers, with an emphasis on achievement of the appropriate lung volume for initiation of the partial maneuver. The child passively exhaled to functional residual capacity and then placed the mouthpiece in his or her mouth and breathed several tidal volume loops on the spirometer. After breathing tidally for several respiratory cycles, the child performed a partial forced expiratory maneuver to residual volume (RV), beginning at an appropriate lung volume (see criteria 1 and 2 below). After maintaining the partial forced expiratory maneuver until a flow rate of zero was reached, the subject then inhaled maximally to total lung capacity (TLC) and performed an FVC maneuver. During these maneuvers, the flow-volume loops were displayed simultaneously on the PC video terminal for viewing by both the technician and the subject.

Our goal was to obtain three maximal/partial (M/P) combined maneuvers (at least two of them reproducible, i.e., FVC within 10%) per subject, with fulfillment of the following four criteria: (1) The volume at which the partial maneuver was started was between 50% and 70% of vital capacity above RV (equal expired volumes were assumed to represent equal lung volumes). (2) The volume at which the partial maneuver reached its peak expiratory flow was between 45% and 65% of vital capacity above RV. (3) The maximal curve passed both American Thoracic Society (ATS) start-of-test and end-of-test criteria. (4) The initial upslope (d/dV) of the partial curve was reasonably parallel with that of the maximal curve. Our methods for the partial expiratory maneuver were consistent with other published reports (4, 8). The computer software program indicated to the technician whether the first three criteria were met, and the technician judged the final criterion by eye. A subject performed a maximum of nine maneuvers to obtain three M/P combined maneuvers that met these four criteria, at least two of which were reproducible. Each subject had to have at least one combined maneuver that met all four criteria to be included in further analyses. From among each subject's acceptable combined maneuvers, the one with the highest sum of FEV₁ + FVC from the maximal curve was used for analysis.

After the data were collected, the flow-volume curves of a random sample of 5% of all children with at least one curve meeting the above four acceptability criteria were reviewed by a pulmonary physiologist (R.H.I.) to ensure the quality of the curves obtained. Three criteria were considered in this review: (1) The ratio of maximal flow rate to partial flow rate was to be constant at low lung volumes below the notch on the partial curve, ensuring that flow limitation had been reached on both the maximal and the partial maneuver and that efforts were comparable on both over this volume range. (2) The initial d/dV of both the maximal and the partial curves were to be steep (by eye) and equal (by measure), ensuring adequate and equal efforts at the beginnings of both maneuvers. (3) Notches were to be present on both the maximal and the partial curve, indicating the onset of flow limitation in the IInd configuration. If a notch were present on one curve and not on the other, the curve without the notch could have flows too high (less gas compression) or too low (not reaching flow limitation). For a maneuver to be considered acceptable in this post hoc review, criterion 1 had to be met in conjunction with either criterion 2 or 3.

The software developed for this project calculated the following parameters for each M/P combined maneuver: FEV₁, FVC, FEV₁/ FVC ratio, _35M, _30M, and _25M from the maximal curve, and _35P, _30P, and _25P from the partial curve. We used the mean of the three instantaneous flow rates (_35M, _30M, _25M) from the maximal curve as the measure of _30M to provide greater reliability than a single instantaneous flow rate. Similarly, the mean of the three instantaneous flow rates (_35P, _30P, _25P) from the partial curve was used as the measure of _30P. The _30M/_30P ratio was used as the measure of volume history in analysis.

Questionnaire

A health questionnaire was sent home early in the school year to be completed by a parent or guardian and returned to school. Each responding parent or guardian was asked whether she or he currently smoked cigarettes and whether a second parent or other "primary adult" smoked. Respondents were asked whether the child had ever been diagnosed by a physician as having asthma, and, if so, whether the child experienced symptoms or took medication for asthma in the past year.

Data Analysis

Version 6.11 of the Statistical Analysis System (SAS) package (9) was used for data analysis. Spirometric indices were compared between maternal smoking or asthma categories, and adjusted means were calculated, using analysis of covariance to adjust for age, height, and community.

	RESULTS

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Among the 2,043 children tested, 1,834 (90%) performed at least one acceptable combined maximal and partial flow-volume maneuver. Two or more acceptable maneuvers were performed by 1,647 (81%) of the children. The 1,834 children who performed at least one acceptable maneuver had an average age of 10.5 yr (Table 1). The parent(s) reported doctor- diagnosed asthma for 13% and 6% of the boys and girls, respectively. Almost one-third of the children had a mother who was a current cigarette smoker. A total of 54 boys (6%) and 27 girls (3%) reported at the time of lung function testing that they used an asthma inhaler, and only 15 of these children reported having used an inhaler within the preceding 12 h.

For both boys (Table 2) and girls (Table 3), children with a history of asthma had lower FEV₁ and expiratory flow rates after adjustment for age, height, and towncode. This difference was most striking and most statistically significant for indices including FEV₁, FEF_25-75, and _30M, although indices including _30P also differed between children with and without asthma. The _30M/_30P ratio did not differ between children with and without asthma. The _30M/_30P ratio was greater among girls than boys (1.26 versus 1.18, p = 0.0001). For boys only, the FVC of children with asthma exceeded that of children without a history of asthma.

Spirometric indices also varied with current maternal smoking status (Tables 4 and 5), although this relation was less striking than for asthma history. Among boys (Table 4), indices including FEF_25-75 and _30M and the FEV₁/FVC ratio demonstrated the largest differences between exposed and nonexposed children. Among girls (Table 5), exposed children had significantly lower levels of FEV₁/FVC, FEF_25-75/FVC, _30M/FVC, and _30P/FVC. Smoke-exposed girls had a slightly but significantly higher level of FVC. Among both boys and girls, the _30M/_30P ratio was not related to maternal smoking status.

Only combined partial and maximal forced expiratory flow-volume maneuvers that were acceptable by the criteria applied at the time of testing were analyzed. The post hoc review of 5% (n = 92) of these "acceptable" curves, however, revealed that only 68 of the 92 (74%) curves reviewed met the more stringent criteria for a adequate combined partial and maximal flow-volume curve. Of the 24 inadequate curves, 23 were flawed by a nonconstant ratio of maximal to partial flow at low lung volumes.

	DISCUSSION

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This analysis of maximal and partial forced expiratory flow measurements in a population-based sample of 10- to 11-yr-old children was undertaken to determine which spirometric measurements are the most sensitive indicators of subtle airways dysfunction in epidemiological investigations. Parent- reported asthma and parental smoking are associated with decrements in lung function in populations of children (10), so we examined the relative ability of various spirometric measurements to detect these effects. The FEF_25-75, the FEF_25-75/ FVC ratio, and the FEV₁/FVC ratio provided the best discrimination between children with and without asthma. The effect of maternal smoking was most striking on the FEV₁/FVC ratio, FEF_25-75/FVC ratio, and _30M/FVC ratio. The influence of a deep inhalation on expiratory flow, as expressed by the _30M/_30P ratio, did not vary with history of asthma or maternal smoking status.

Persons with airflow obstruction related to asthma have a wide range of volume history effects, varying from quite low values of maximal/partial flow rate (i.e., increased obstruction after a deep inhalation) to high values (i.e., decreased obstruction after a deep inhalation) (4) depending on the mechanism of obstruction. With spontaneous obstruction related to airway inflammation, there is a consistently low volume history ratio in direct relationship to the degree of obstruction (4) and the intensity of peripheral inflammation (5). With obstruction induced by airway smooth muscle constrictors there is a consistently increased volume history ratio in direct proportion to the magnitude of the induced obstruction (1, 2). These opposite volume history effects have been related to disparities between parenchymal and airway hysteresis (13).

Our initial hypothesis that volume history effects might differ between children with and those without subtle airways abnormalities is not supported by the current findings. Neither a history of asthma nor maternal smoking, both of which were associated with decrements in spirometric measurements, were associated with alterations of the _30M/_30P ratio. Clearly, however, the absolute flow rates of both the _30M and _30P were significantly lower. The children with asthma identified in this population sample are likely to have less severe asthma on average than would be seen in a clinical referral setting. It remains possible that children with severe asthma would have a reduced _30M/_30P ratio compared with children with less severe asthma and the general population.

Although many spirometric indices revealed significant effects of asthma and maternal smoking, the FEF_25-75/FVC ratio was particularly consistent as a measurement that discriminated both of these effects in both boys and girls. The FEF_25-75 is believed to be a measure that is more sensitive to peripheral airways pathology than is FEV₁ (16). Rather than correct for lung size indirectly by adjusting for age and height, a more direct correction for lung size by dividing the FEF_25-75 by FVC may provide an optimal measurement for detecting subtle airways abnormalities in epidemiological studies of children.

A limitation of this study is that the post hoc review of flow-volume curves revealed a disappointingly high (24%) proportion of suboptimal combined maximal-partial flow- volume curves. Both in terms of software development and technician training, however, a great deal of effort was put into obtaining the highest possible quality of combined maneuvers, and it is unlikely that better quality flow-volume curves could be obtained from children of this age group tested in a nonlaboratory setting. It is not feasible to perform post hoc review of the curves of all 1,834 children, so we cannot rule out the possibility of between-group differences in test quality. Another potential limitation is our reliance on expired volume to determine the lung volume at which maximal and partial flow rates were measured. Although this method is potentially susceptible to thoracic gas compression artifacts that may differentially affect maximal and partial curves and that may be more pronounced in persons with substantial airflow obstruction, such gas compression effects have been shown to be have minimal impact on estimates of the ratio of maximal to partial expiratory flow rates in healthy persons and persons with asthma (17).

In conclusion, both maternal smoking and the report of a history of asthma were associated with reduced spirometric indices in a population-based sample of 10- to 11-yr-old children. Measurements derived from a maximal forced vital capacity maneuver provided better discrimination of these effects than measurements derived from a partial forced expiratory maneuver. The effect of volume history on expiratory flow rates did not differ between children exposed and children not exposed to maternal smoking, nor among those with or without a history of asthma. The ratio of FEF_25-75 to FVC was a particularly consistent measurement for detecting the effects of asthma and maternal smoking.