Spirometric values in children and adolescents with short stature

ORIGINAL ARTICLE

Spirometric values in children and adolescents with short stature^*

Naiza Alessandra Dorneles^I; Nelson Augusto Rosário Filho^I; Carlos Antônio Riedi^I; Margareth Cristina Boguszewski^II; João Adriano de Barros^III (te sbpt)

^IDivision of Pediatric Respiratory Medicine

^IIPediatric Endocrinology Unit

^IIIDepartment of Internal Medicine. Certified by the Brazilian Society of Pneumology and Tysiology.

^{Correspondence}

ABSTRACT

BACKGROUND: Several factors influence the pulmonary function values considered normal. In children of short stature, there are difficulties in interpreting the pulmonary function.

OBJECTIVE: To assess spirometric values in children and adolescents with short stature and to identify a correction factor to adequately predict the expected values for this population.

METHOD: Aprospective selection of 77 patients was made, all with short stature and no respiratory disease. These patients were submitted to spirometry, transcutaneous hemoglobin oxygen saturation, chest perimeter measurement, and immediate hypersensitivity testing. Bone age was assessed by wrist X-rays. The data obtained by spirometry (FVC, FEV₁, and FEF_25-75%) were compared with those of Polgar and Promadhat (1971), predicted in three ways: a) by actual height; b) by height estimated at the 50^th percentile for chronological age (CA); c) by height estimated at the 50^th percentile for bone age (BA).

RESULTS: The mean height was 133.3 ± 13.2 cm, and the deficit in relation to the third percentile was 5.4 ± 6.0 cm. The values obtained for FVC, FEV₁, FEF_25-75%, were significantly higher than those predicted by actual height. The mean FEV₁ obtained was 2.42 ± 0.71 L, and the predicted (actual height) was 2.10 ± 0.64 L; according to the height estimated by BA and CA, the values were 2.27 and 2.86 L, respectively. The mean FVC₁ was 2.20 ± 0.6 L, and the predicted was 1.90 ± 0.55 L. With the height estimated for bone age and chronologic age, the predicted values were 2.10 and 2.60 L, respectively.

CONCLUSION: Children and adolescents with short stature have higher spirometric values than predicted for their actual height. These findings suggest that the height estimated at the 50^th percentile for bone age can be used to evaluate pulmonary function.

Key words: Lung function. Short stature.

Acronyms and abbreviations used in this study

TPC – Total pulmonary capacity

FVC – Forced vital capacity

WHD – Weight-Height deficit

FEF_25-75% – Mean forced expiratory flow for the segment of FVC maneuver

PF – Pulmonary function

CA – Chronologic age

BA – Bone age

PTB – Premature newborn

TNB – Term newborn

ST – Immediate cutaneous hypersensitivity test

FEV₁ – Forced expiratory volume in one second

Introduction

Spirometry is one of the technics to assess pulmonary function and despite an apparent simplicity it involves details that influence analysis and interpretation ⁽¹⁾ therefore it should be performed using clinical and epidemiologic data. ^(2,3)

Results of pulmonary function are influenced by many factors: gender, stature, race, age, technical factors, weight, and others.^(2,4) Before test results are considered abnormal, technical and biologic variations must be taken into account.^(5,6) Gender and stature are the most important determinant factors, taking this into account reference tables were compiled. However, since they do not include extremes of stature, ⁽⁷⁾ assessment of values from subjects outside the normal range becomes more difficult.

Factors such as overweight,⁽⁸⁾ thoracic deformities, cardiac diameter,⁽⁹⁾ and skeletal changes⁽¹⁰⁾ may influence the results of pulmonary function tests, but many of these conclusions were reached for adults or restricted populations. There is little information available concerning children.

Because interpretation of spirometry data in asthmatic children and adolescents with stature deficit is difficult. This study was carried out to assess if changes in the spirometric values are detected for short stature patients and also to identify a factor of correction that can be applied to the existing reference values.

Methods and subjects

A prospective study was carried out from May to October, 2000. Children of both genders, aged ³ 6 years treated at the Outpatient Pediatric Endocrinology Unit due to constitutional short stature or hypophysiary nanism, able to perform a pulmonary function test, were included. Since sample size had not been stipulated; it was determined after initial screening of 150 short stature patients, with exclusion of those who did not meet the criteria.

Excluded were subjects who presented with acute respiratory disorders in the previous four weeks, or chronic respiratory disorders, genetic syndromes, birth defects or previous thoracic surgery.

The medical history of selected children and adolescents was documented. They were submitted to physical exams, thoracic perimeter measurement at tidal volume, immediate hypersensitivity skin tests, spirometry, and wrist x-ray for bone age determination (Greulich-Pyle).⁽¹¹⁾ Medical history included a questionnaire with information about: obstetric background (respiratory distress at birth, need of ventilatory assistance, lung diseases, such as asthma, bronchopulmonary dysplasia, or cystic fibrosis, diagnosed by a physician, nasal and cutaneous allergy symptoms, personal or familial smoking addiction). Smoking, even passive, might cause decrease in FEV values due to airway obstruction. All these matters were reviewed to eliminate eventual bias in the study

As a complement to the physical exam, weight (Filizola scale), stature (Tonelli’s Stadiometer), thoracic perimeter measurement (measured with a tape at the nipples, independent of the respiratory phase) and presence of thoracic deformities were assessed.

For allergy skin tests, house dust mite allergenic extract (D. pteronyssinus 5.000UA Hol­lister-Stier USA, Blomia tropicalis, IPI-ASAC do Brasil) were used with a positive histamine control (10mg/mL concentration) and a negative control with saline. The test technique consisted of a puncture with a BD 13 x 4.5 needle for each patient and different for each stratum. A reaction was considered positive with the presence of a ³ 3mm wheal as compared to saline, for one or both substances. ⁽¹²⁾

Spirometry was performed at the Pulmonary Function Laboratory, according to the reproducibility criteria of the American Thoracic Society (ATS) on a volume Collins-USA (Survey Plus) spirometer with automatic correction of the values to BTPS (body temperature, ambient pressure water vapor saturated) ⁽¹³⁾ All tests were performed before 10 o’clock in the morning, on the same device. For test, subjects remained seated,⁽¹⁴⁾ with a nasal clip,⁽¹⁵⁾ the head was maintained in a neutral position to avoid flexion or extension which respectively decrease and increase initial forced expiratory flows.⁽¹⁶⁾ For the bronchodilator test, salbutamol aerosol was used, at a dose of 100µg x 4 puffs with a 30 second interval between puffs. Spirometry was repeated 15 minutes after bronchodilator inhalation. The table for reference values was that of Polgar and Promadhat (1971) ⁽²⁾. Hemoglobin transcutaneous oxygen saturation was obtained with a pulse oximeter 1000, Moriya.

Pre-bronchodilator values were FVC, FEV₁, FEF_25-75%, and FEV₁/FVC, according to the subject’s actual anthropometric data. Other predicted values were reached in two ways: by stature in the 50^th percentile for chronologic age and for bone age .Results obtained were then compared with three predicted values (actual stature, stature for BA, and stature for CA) and the value nearer to the obtained values was assessed.

A descriptive data analysis was performed using tables, figures, and graphs. In order to verify the objectives of this study, the non-parametric test, multiple regression analysis, proportions comparison, and chi-square, were used for paired samples using the Primer of Bioestatistics software. The level of significance adopted was 5%.

The study protocol was approved by the Ethics Committee of the Hospital de Clínicas-UFPR, and parents, or legally responsible persons, provided a signed informed consent.

Results

Of the 77 children (48M : 29F) studied, 55 had a familial statural deficit (SD), 17 had hypophysiary nanism, and five had other diagnoses. Sixty-eight children had been term newborns (TNB), and nine had been premature babies (PTB).In the PTB group the exact gestational age could not be determined, but none needed oxygen or presented respiratory problems at birth.

The mean age was 12.4 ± 2.7 years; mean stature was 133.3 ± 13.2cm; mean weight was 30.9 ± 8.5kg; and mean thoracic perimeter was 65.9 ± 5.7cm. Figure 1 shows the distribution by age, with a two year interval.

Subjects had average stature 5.4 cm below the 3^rd percentile. Table 1 shows the descriptive analysis of the children’s anthropometric data.

For the actual stature of males, mean values of predicted FVC, FEV₁ and FEF_25-75% were, respectively, 2.1 ± 0.69L, 1.8 ± 0.59L, and 2.4 ± 0.69L. For females, means of the same values were 2.1 ± 0.53L, 1.9 ± 0.48L, and 2.3 ± 0.59L. Mean of the values for males was 2.4 ± 0.78L for FVC, 2.2 ± 0.72L for FEV ₁ and 2.6 ± 0.97L for FEF_25-75% and for females, 2.3 ± 0.58L, 2.1 ± 0.53L and 3.0 ± 0.82L, respectively.

Mean values for FVC, FEV ₁ and FEF_25-75% for the whole group were, respectively, 14.3%, 15.8% and 21.7% higher than the normal reference values for stature of subjects (p < 0,05).

When estimated stature for the 50^th percentile for chronologic age was used, predicted values for males were: FVC = 2.9 ± 0.73L, FEV ₁ = 2.6 ± 0.70L and FEF_25-75% = 3.3 ± 0.71L; for females: FVC = 2.7 ± 0.59L, VEF₁ = 2.6 ± 0.57L and FEF_25-75% = 3.3 ± 0.64L. Similarly, when stature was estimated according to bone age, predicted values for males were: FVC = 2.3 ± 0.70L, FEV ₁ = 2.0 ± 0.67L, and e FEF_25-75% = 2.6 ± 0.83L, and for females, 2.2 ± 0.55L, 2.1 ± 0.54L and 2.6 ± 0.69L, respectively. Thus resulting values were compared to three predicted values. Table 2 shows the mean of obtained and predicted spirometry data for both genders. Obtained FVC, FEV ₁ and FEF_25-75% values were significantly higher than those predicted for actual stature, CA 50^th percentile stature, and BA 50^th percentile stature (p < 0.05), except for predicted BA FEF_25-75%. Figure 2 is a box plot of the distribution of obtained and predicted spirometry values.

Immediate hypersensitivity skin tests were positive in 21 boys and five girls. Of 26 children with positive ST, 13 had allergic symptoms, primarily nasal pruritus, sneezing and ocular pruritus. Thirteen were asymptomatic, and of the negative ST children, 38 had no allergic symptoms. There was no correlation between the presence of symptoms and response to ST (c²= 1.08; p = 0.29).

The correlation between thoracic perimeter and mean obtained values of FVC, FEV ₁ and FEF_25-75% was statistically significant(r = 0.7; p £ 0.001). It was noted that subjects with values above the mean also had a thoracic perimeter measurement above the age percentile.

Multiple regression analysis for variables such as stature, weight, thoracic perimeter, and age showed that stature is the most significant variable for establishing parameters of pulmonary function.

Passive or active smoking was found in 39 of the 77 children under study, and there was no statistically significant difference between both groups. The 13 children who had nasal symptoms and a positive ST were included in this group (smoking). After salbutamol inhalation, bronchodilator response with a 12% increase in FEV was noted in five male subjects, three of which had a positive ST, and one had nasal symptoms. There was a variation of 95 to 98% in the oxygen transcutaneous hemoglobin as measured by non-invasive oximetry.

Discussion

Lungs of a newborn are not miniature lungs of an adult ⁽¹⁷⁾ Knowledge of the changes that take place according to the child’s age is required to understand variations in pulmonary function between children and adults, boys and girls, and healthy subjects and patients with pulmonary diseases. Thurlbeck ⁽¹⁸⁾ described the anatomy of pulmonary growth and concluded that girls have lower pulmonary volumes than boys with the same stature. The relationship between body size and spirometry values also changes with age.^(4,18) After birth, each structural component of the respiratory system has different pattern of growing with relative increase of size and number.⁽¹⁹⁾ Residual functional capacity increases from about 80mL at birth to approximately 3,000mL in adulthood ⁽¹⁷⁾ while lung weight increases from 60 to 750 grams.⁽⁴⁾ Many authors agree that in terms of size, airways and lungs have a non-proportional development.⁽²⁰⁾ Others believe that growth is isotropic.⁽²¹⁾ The body size measure had a direct influence on the pulmonary volume whereas factors that determine geometry of the airways have a greater influence on airflow variation.⁽²²⁾

Growth of body and lungs during childhood is proportional but without a linear relationship between them. ^(2,3) Stature is the most influential factor on the vital capacity in childhood and this relationship is better described by exponential equations. In childhood, rates FEV₁/FVC and flow/FVC are still relatively constant although slightly lower for boys. ⁽¹⁾

In this study, the assessment of stature in relation to pulmonary function was the factor taken for the interpretation of the results obtained. As such, obtained values were compared to predicted values, taking in consideration the reference tables since stature is the most relevant variable. Obtained values were higher than predicted values. Based upon this, two changes in terms of the height used for calculation of predicted values were introduced. The first was the use of CA 50^th percentile stature and the second was the use of BA 50^th percentile stature.

Bone age is the best parameter for growth velocity and can be used to estimate final adult height. Variations in bone age are related to the biologic activity of sexual steroids. Height may be predicted by several methods and more accurately with epiphysis fusion. ⁽²³⁾

Values of pulmonary function considered normal rest upon factors such as: height, gender, weight, technique adopted, etc. Pulmonary function may be different for subjects of the same gender, similar age and stature. These values may be analyzed by: 1) central trend measurements, such as mean and median; 2) dispersion measurements, such as standard deviation; and 3) symmetry of distribution according to some mathematical index. ⁽²⁴⁾ By regression analysis, it could be seen that stature was the most important factor for spirometry, further that active or passive smoking did not affect results and so did not contribute to the observed differences.

Some studies show that in children there is no standard for adjustment of the pulmonary function values according to age or stature. A multiple regression could not be used for transformation of the findings because for instance FEV₁ which is normally distributed by stature, age and gender has an increased standard deviation. After logarithmic transformation of FEV₁, the standard deviation was constant. The rate of actual and predicted values had a normal distribution in boys. ⁽²⁵⁾

For Aitken et al, ⁽²⁶⁾ predicted values of pulmonary function may be extended to include those above the 99^th percentile, or under the 5^th percentile for stature, using the same linear regression equation. These authors state that pulmonary and airway growth may not be proportional. Therefore, subjects with large lungs may not necessarily have large airways.

Longitudinal studies offer the best approach to establish a relation between age and pulmonary growth. An Australian cohort with eight year-old subjects was studied. every second year until the age of 17-19 years. At the time of the last test, linear growth had stopped, but FEV1 continued to increase some 200mL/year for males and 100mL/year for females. ⁽²⁷⁾

Total pulmonary capacity (TPC) reflects pulmonary size while FEV₁ and FEF_25-75% reflect dimension of the airways. In the present study, these parameters were higher than predicted, supporting the hypothesis that somatic development does not accompany visceral growth. For this study the table of values by Polgar and Promadhat⁽²⁾ was used, because its curves overlay those of the Pneumobil Program and is countersigned by the Guidelines for Pulmonary Function Tests 2002.⁽¹⁾

Thoracic dimensions grow more in length than in width.⁽²⁸⁾ A study with men from 16 to 23 years of age showed that thoracic perimeter and stature are the best predictors for vital capacity and FEV₁⁽²⁹⁾; however in this study measure of the thoracic perimeter showed no correlation with stature or FEV ₁.

Allergy skin tests were introduced to investigate if atopy and asthma might be detected and could interfere with the pulmonary function tests, even for subjects without a clinical history suggesting atopy. Despite response to a short acting bronchodilator, positive cutaneous test, and symptoms of rhinitis, values of the pulmonary function were higher than expected, showing that these variables, contrary to the expected, did not affect results.

Short stature makes it difficult to interpret spirometry in patients with airways obstruction because predicted values for normal subjects do not apply to this group of patients. The study data shows that reference tables for spirometry should be modified and that the stature estimated in the 50^th percentile for bone age is an alternative to arrive at the predicted values for subjects with a stature deficit.

Received for publication on 29/01/02

Approved, after review, on 22/04/03

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*

This study was performed at Hospital de Clínicas, Federal University of Parana, Curitiba, PR.

Publication Dates

• Publication in this collection
  02 Dec 2003
• Date of issue
  Aug 2003

History

• Accepted
  22 Apr 2003
• Received
  29 Jan 2002