Sniff Nasal Inspiratory Pressure Reference Values in Caucasian Children

Sniff Nasal Inspiratory Pressure Reference Values in Caucasian Children DANIELA STEFANUTTI and JEAN-WILLIAM FITTING Division de Pneumologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland Like in adults, normal values of maximal inspiratory pressure (PI max ) and maximal expiratory pressure (PE max ) span a large range in children, making interpretation of low values difficult. Recently, sniff nasal inspiratory pressure ( ) was developed as a new noninvasive test of inspiratory muscle strength. In healthy adults, is most often higher than PI max. The aim of this study was to establish reference values of in children and to compare them with PI max. A group of 180 unselected healthy children age 6 to 17 yr was studied in a school setting. All had a forced vital capacity (FVC) 80% of predicted and a ratio of forced expiratory volume in one second/forced vital capacity (FEV 1 / FVC) 85% of predicted. All maneuvers were performed in the sitting position. The was measured using a catheter occluding one nostril during maximal sniffs performed through the contralateral nostril from FRC. The PI max was measured from FRC and residual volume, and PE max from FRC and total lung capacity. All children were able to perform the maneuver easily. was 104 26 cm H 2 O in boys and 93 23 cm H 2 O in girls (p 0.005). These values were similar to those previously measured in healthy adults. correlated with age, weight, and height in boys, but not in girls. In both sexes, was higher than PI max measured at the same lung volume (FRC) (p 0.0001). was PI maxfrc in 73 of 93 boys and 79 of 87 girls. We conclude that can be easily used to assess inspiratory muscle strength in children age 6 yr or more, providing values higher than PI max. Normal values are independent of age in girls, and can be predicted from age by a first-degree equation in boys. Being easy and noninvasive, may prove useful to assess inspiratory muscle strength in children with neuromuscular disorders. Stefanutti D, Fitting J-W. Sniff nasal inspiratory pressure: reference values in Caucasian children. AM J RESPIR CRIT CARE MED 1999;159:107 111. The measurement of respiratory muscle strength is important in children with neuromuscular or skeletal disorders. In the presence of a neuromuscular disease, respiratory muscle strength can be reduced when lung volumes are still in the normal range. Conversely, in case of scoliosis respiratory muscle strength can be normal in spite of reduced lung volumes (1). Furthermore, interventions such as inspiratory muscle training in neuromuscular patients may improve inspiratory muscle strength, but not lung volumes (2). The classic tests of respiratory muscle strength are maximal inspiratory pressure (PI max ) and maximal expiratory pressure (PE max ) developed volitionally against a near complete occlusion (3). In children, these pressures were found to be relatively close to those of adults (4 7). However, as in adults, the inferior limits of normal values are low for PI max and PE max, in particular in young children, probably reflecting the difficulty of these maneuvers for some subjects. To obviate this problem, several tests of inspiratory muscle strength have been developed based on the sniff, which is a (Received in original form April 7, 1998 and in revised form August 10, 1998) Supported by a grant from the Swiss Thoracic Society. Correspondence and requests for reprints should be addressed to Dr. J. W. Fitting, Division de Pneumologie, CHUV, CH-1011 Lausanne, Switzerland. Am J Respir Crit Care Med Vol 159. pp 107 111, 1999 Internet address: www.atsjournals.org natural and easy maneuver (8, 9). The sniff nasal inspiratory pressure ( ) is a new noninvasive test. It consists of measuring nasal pressure in an occluded nostril during a maximal sniff performed through the contralateral nostril, and has been validated in adults (10). Normal values were established for in healthy adults, and were most often higher than PI max (11). The aims of this study were to assess the feasability of, to establish reference values, and to compare them with PI max in a large group of unselected healthy children. METHODS Subjects A total of 203 children of a school in the Lausanne area, located in a middle-class suburb, participated in this study. For each grade, one class was included and all children were asked to participate. Consent was obtained from parents who also completed a short medical questionnaire. The study was approved by the ethics committee of the Faculty of Medicine, University of Lausanne. Twenty-three children were excluded from analysis for the following reasons. Seven were of non-european descent. Thirteen had an abnormal spirometry: forced vital capacity (FVC) 80% of predicted value or forced expiratory volume in one second to forced vital capacity ratio (FEV 1 /FVC) 85% of predicted value. Two children were currently treated for asthma and one had a metabolic disease. Finally, 180 children were included in the study. All were Caucasians, and none was suffering from a known metabolic, neuromuscular, or cardiac disease. Twelve children with known asthma were in-

108 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 159 1999 TABLE 1 RELATIONSHIPS BETWEEN RESPIRATORY PRESSURES AND AGE AND GROWTH PARAMETERS Boys Girls Age Height Weight Age Height Weight r 0.36 r 0.32 r 0.38 NS NS NS p 0.0005 p 0.005 p 0.0001 PI maxfrc r 0.63 r 0.61 r 0.62 r 0.38 r 0.33 r 0.33 p 0.0001 p 0.0001 p 0.0001 p 0.0005 p 0.005 p 0.005 PI maxrv r 0.59 r 0.57 r 0.59 r 0.25 r 0.22 r 0.28 p 0.0001 p 0.0001 p 0.0001 p 0.05 p 0.05 p 0.01 PE maxfrc r 0.49 r 0.43 r 0.51 NS NS r 0.21 p 0.0001 p 0.0001 p 0.0001 p 0.05 PE maxtlc r 0.52 r 0.48 r 0.54 r 0.28 r 0.25 r 0.32 p 0.0001 p 0.0001 p 0.0001 p 0.01 p 0.05 p 0.005 cluded because they had a normal spirometry and were not currently receiving antiasthmatic therapy. All children were studied at a time when they were free of upper airway infection, because loses its validity in cases of marked nasal congestion (10). Experimental Protocol All measurements were performed by the same investigator in a single session for each subject. Height and weight were measured and body mass index (BMI) was calculated as weight/height 2. After a brief instruction on the different tests, the investigator measured, PI max, PE max, and spirometry. All measures were taken in the sitting position. was measured in an occluded nostril during a maximal sniff performed by the contralateral nostril (10). The plug was made of waxed ear plugs (Calmor, Neuhausen am Rheinfall, Switzerland) hand-fastened around the tip of a catheter (internal diameter, 1 mm; length, 100 cm). The catheter was connected to a hand-held pressure meter displaying peak pressure (Pmax Mouth Pressure Monitor; P. K. Morgan, Rainham-Gillingham, Kent, UK). was measured during 10 maximal sniffs performed from FRC, each separated by 30 s. All maneuvers were recorded and the highest pressure was considered. The PI max was measured using a standard flanged mouthpiece connected to a hand-held pressure meter computing average pressure sustained over 1 s (Mouth Pressure Meter; P. K. Morgan). The subjects were studied with their nose occluded with a noseclip. They were asked to perform five maximal inspiratory efforts from FRC, each separated by 30 to 60 s. PI max was then measured from residual volume (RV) according to the same technique. Similarily, PE max was measured during five maximal expiratory efforts from both TLC and FRC. Care was taken to eliminate any air leak around the mouthpiece. For each test, all trials were recorded and the highest pressure was considered. Spirometry was measured with a portable device (Multispiro SA/ 100; Medical Equipment Designs, Laguna Hills, CA), which was calibrated before each session with a 3-L syringe. The subjects had their nose occluded by a noseclip. Three to eight forced expiratory maneuvers were performed until the difference between the best two trials (sum of FEV 1 and FVC) was inferior to 5%. The predicted equations of Polgar were used (12). Data Analysis For each sex, data were expressed as means, SD, and range. When pressures were related to age, they were also presented in two age groups, from 6 to 12 yr and from 13 to 17 yr. Linear regression analysis was used to assess the relationships between respiratory pressures (, PI max, PE max ) and age, height, and weight. was compared between boys and girls, and between boys 6 to 12 yr and 13 to 17 yr using two-tailed unpaired t tests. and PI max were compared using two-tailed paired t tests. The agreement between and PI max was assessed by the method of differences against the means according to Bland and Altman (13). The coefficient of variation was used to express the within-session reproducibility of, PI max, and PE max. RESULTS Anthropometry All boys were within the normal growth curves for height and weight for Swiss children (14), except one above the 97th percentile for weight. All girls were within the normal growth curves, except two above the 97th percentile for weight, two above the 97th percentile for height, and one above the 97th percentile for height and weight. In boys, the BMI was 17.3 2.5 kg/m 2 (range, 12.6 to 23.8 kg/m 2 ). In girls, the BMI was 17.8 2.8 kg/m 2 (range, 13.1 to 24.5 kg/m 2 ). The maneuver was performed by all children without difficulty. Considering the entire groups, was 104 26 cm H 2 O in boys and 93 23 cm H 2 O in girls (p 0.005). In boys, correlated with age, height, and weight (Table 1). The prediction equation in boys is: 3.3 age 70; residual standard deviation 24.3. Subtracting 1.64 residual standard deviation from the predicted value will provide the lower limit above which lie 95% of normal boys. was higher in boys 13 to 17 yr than in boys 6 to 12 yr (p 0.005; Table 2). In girls, did not correlate with age, height, or weight (Table 1). The relationship between and age in boys and girls is presented in Figure 1. The mean within-session coefficient of variation of was 16.2% in boys and 17.0% in girls (Table 3). PI max and PE max In boys 6 to 17 yr, the mean values were 88 24 cm H 2 O for PI maxfrc, 94 23 cm H 2 O for PI maxrv, 87 26 cm H 2 O for PE maxfrc, and 103 27 cm H 2 O for PE maxtlc. All pressures TABLE 2 RESPIRATORY PRESSURES IN BOYS AND GIRLS* n PI maxfrc PI maxrv PE maxfrc PE maxtlc Boys, 6 to 12 yr 67 99 22 80 20 88 19 80 24 96 24 55 155 38 134 48 141 37 147 55 159 Boys, 13 to 17 yr 26 117 31 107 22 110 23 105 23 123 22 70 186 66 153 60 152 56 145 91 162 Girls, 6 to 12 yr 63 92 22 68 17 77 19 65 22 80 22 51 151 32 109 38 124 28 119 37 137 Girls, 13 to 16 yr 24 97 26 81 20 86 21 74 23 91 24 55 155 54 131 53 137 42 142 53 155 * Values are means SD and range.

Stefanutti and Fitting: Sniff Nasal Inspiratory Pressure in Children 109 Figure 1. Relationship between and age in boys and girls. correlated with age, height, and weight (Table 1). In girls 6 to 16 yr, the mean values were 72 19 cm H 2 O for PI maxfrc, 79 20 cm H 2 O for PI maxrv, 68 23 cm H 2 O for PE maxfrc, and 83 23 cm H 2 O for PE maxtlc. All pressures correlated with age, height, and weight, except PE maxfrc, which did not correlate with age or height (Table 1). For boys and girls, the pressures are presented according to age groups in Table 2. The mean within-session coefficients of variation of PI max and PE max are presented in Table 3. In both sexes, was higher than PI max measured at the same lung volume (FRC) (p 0.0001). The value of was n TABLE 3 COEFFICIENTS OF VARIATION OF RESPIRATORY PRESSURES IN BOYS AND GIRLS* PI maxfrc PI maxrv PE maxfrc PE maxtlc Boys 93 16.2 6.7 12.1 7.0 12.6 6.9 14.1 8.2 14.2 7.9 Girls 87 17.0 6.7 15.4 9.2 12.8 6.4 15.7 9.6 15.1 7.2 * Values are means SD. Figure 2. Relationship between and PI max measured at functional residual capacity (PI maxfrc ) in boys and girls. The line represents the line of identity. higher or equal to PI maxfrc in 73 of 93 boys and 79 of 87 girls (Figure 2). In boys, the mean difference PI maxfrc was 16.6 20.4 cm H 2 O, and the limits of agreement were 57.4 cm H 2 O and 24.2 cm H 2 O. In girls, the mean difference PI maxfrc was 21.6 18.6 cm H 2 O, and the limits of agreement were 58.8 cm H 2 O and 15.6 cm H 2 O (Figure 3). DISCUSSION The main findings of this study performed in healthy children were: (1) without exception, could be measured easily in a large group of unselected children ranging in age from 6 to 17 yr; (2) correlated positively with age, height, and weight in boys, but not in girls; (3) in both sexes, was

110 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 159 1999 Figure 3. Difference between and PI max measured at functional residual capacity (PI maxfrc ) against the mean of these two variables in boys and girls. higher than PI max ; and (4) values were similar to those previously measured in normal adults (11). Recently, several tests of inspiratory muscle function have been developed on the basis of the sniff maneuver, which is both easy to perform and reproducible (8, 9). In particular, the has the advantage of being entirely noninvasive and has been validated in normal adults and in patients (10, 11, 15). This study shows that can be used in children as well. Indeed, they all performed the maneuver easily and nasal pressure could be measured without difficulty in spite of the small size of their nostrils. The within-session coefficients of variation were higher than those previously reported in adults (16), but this was true both for and for PI max. We found that correlated with age, height, and weight in boys, but not in girls. This observation may reflect the greater increase of muscle mass in boys, in particular after puberty. The relationship between inspiratory muscle strength, as measured by PI max, and anthropometric data in children varies in different studies. In children age 7 to 13 yr, Gaultier and Zinman (4) reported that PI max correlated with age and height both in boys and girls, whereas Smyth and coworkers (5) found no correlation between PI max and age, height, or weight in adolescents of both sexes. In children age 7 to 17 yr, Wilson and coworkers (7) reported that PI max was related to weight in boys and girls. Our data of are similar to those of PI max reported by Wagener and coworkers (6). In a group of children of similar age, these investigators found that PI max correlated with age and height in boys, but not in girls. In both sexes, PI max correlated with arm muscle area, as derived from arm circumference and triceps skinfold thickness. In accordance with a previous study in adults (11), we found that was higher than PI max measured at the same lung volume, i.e., FRC. This difference appeared even more clearly as equaled or exceeded PI max in 152 of 180 children (84%), compared with 107 of 160 adults (67%) (11). As in adults, this difference is likely explained by the ease of the sniff maneuver when compared with the PI max maneuver. The natural and painless character of the sniff probably allows the subjects to reach a maximal activation of inspiratory muscles more easily. Such higher activation would compensate for the force loss resulting from the dynamic character of the sniff. Another difference between the two maneuvers lies in the degree of recruitment of the different muscles. In adults, at least, the diaphragm is activated more during a sniff than during a PI max maneuver (17). Finally, the difference observed between and PI max in the present study cannot be ascribed to low values of PI max. Indeed, PI max values were slightly higher than those previously reported in children of similar age (4 7). The values of in children were similar to those that we previously measured in healthy adults (11). Thus, mean was 99 and 117 cm H 2 O in boys age 6 to 12 yr and 13 to 17 yr, respectively, and 111 cm H 2 O in men age 20 to 65 yr. Similarly, mean was 93 cm H 2 O in girls age 6 to 16 yr and 87 cm H 2 O in women aged 20 to 65 yr. This similarity could relate to properties of maximal respiratory pressures in general, and/or to specific characteristics of. In our study, PI max increased with age in both sexes. In the adolescent groups, PI max values were similar to those that we previously measured in adults (11). Thus, mean PI maxfrc was 107 cm H 2 O in boys age 13 to 17 yr and 106 cm H 2 O in men age 20 to 65 yr. Similarly, mean PI maxfrc was 81 cm H 2 O in girls age 13 to 16 yr and 83 cm H 2 O in women age 20 to 65 yr. In contrast, PE max was slightly lower in adolescents, in particular in boys, than in previously studied adults (11). This different evolution of PI max and PE max according to age has been previously reported by Wagener and coworkers (6). In general, PI max and PE max in children have been found either similar to or only slightly lower than in adults (4 7). This is in contrast with other indices of muscle strength and is explained by the fact that a pressure is the ratio between a force and the surface to which it is applied. If respiratory muscle mass increases in proportion with the surface of the thorax, high respiratory pressures are expected to be generated by children in spite of a lower muscle mass (18). Recent autopsy data confirm that diaphragm mass is linearly related to age and height in childhood (19). The similarity of between children and adults may also be related to specific characteristics of this method. probably reflects diaphragm strength predominantly, because this muscle is activated more than other inspiratory muscles during the sniff maneuver (17). Infants are able to develop high transdiaphragmatic pressures (Pdi) during inspiratory efforts while crying against an occluded airway. During this maneuver, Pdi increases with age and reaches a plateau of about 85 cm H 2 O by the age of 6 mo (20). This value is close to the average Pdi measured during pure inspiratory effort in normal

Stefanutti and Fitting: Sniff Nasal Inspiratory Pressure in Children 111 young adults (116 cm H 2 O) (21). The diaphragm appears therefore particularly suited to generate high pressures independent of its actual muscle mass. McCool and coworkers (22, 23) recently explored the relationships between diaphragm structure and its pressure-generating capacity. They considered the diaphragm as a piston acting axially in the thoracoabdominal cavity. In this model, the transdiaphragmatic pressure is determined by the following variables: Pdi CSA di / A thor, where is the tensile stress developed by the contractile elements, CSA di is the cross-sectional area of the diaphragm, and A thor is the axially projected area of the diaphragm. Mc- Cool and coworkers used ultrasound to measure diaphragm thickness at the upper level of the zone of apposition while the subjects were at FRC. The diaphragm cross-sectional area was calculated as the product of diaphragm thickness and circumference. In adults, either untrained or trained weightlifters, Pdi max correlated with diaphragm thickness and cross-sectional area, as well as with the ratio CSA di /A thor. Studying children age 6 to 12 yr and untrained adults, they found that diaphragm thickness, circumference, and cross-sectional area increased with height and weight. Similarly, the axially projected area of the diaphragm increased with height and weight. As a result, the ratio CSA di /A thor remained almost stable among individuals of different sizes. Based on these data, it was calculated that for a given tensile stress, Pdi would increase by only 27% from the smallest child to the heaviest adult in this study (22, 23). The method is based on the fact that the nasal flow limiting segment collapses during a sharp sniff (24, 25). As a result, only a small pressure gradient exists between the upper airways beyond the point of collapse and the intrathoracic cavity. Nasal resistance is higher in children and decreases with age (26). It can be hypothesized that the nasal collapse during sniffs is more complete in children, and that reflects intrathoracic pressure even more closely than in adults. However, were this to occur, the possible pressure gain would be small because represents on average 92% of sniff esophageal pressure in adults (10). Thus the higher nasal resistance of children cannot explain by itself the similarity of between children and adults. Caucasian children only were included in this study because of potential ethnic differences in muscle strength and nasal configuration. The pressure values measured in six children of Asian origin and one of African origin were within the range of values of Caucasian children. The was close to PI max in the four children of Laotian descent and in the two of Indian descent. However, was markedly lower than PI max in the only child of African descent. 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