relationship with anthropometric indices and respiratory symptoms, reference values for dynamic spirometry

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DISSERTATIONES MEDICINAE UNIVERSITATIS TARTUENSIS 64

LUNG FUNCTION

IN ESTONIAN SCHOOLCHILDREN:

relationship with anthropometric indices and respiratory symptoms,

reference values for dynamic spirometry

JANA KIVASTIK

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D IS S E R T A T IO N E S M E D IC IN A E U N IV E R SIT A T IS T A R T U E N SIS

64

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DISSERTATIONES MEDICINAE UNIVERSITATIS TARTUENSIS 64

LUNG FUNCTION

IN ESTONIAN SCHOOLCHILDREN:

relationship with anthropometric indices and respiratory symptoms,

reference values for dynamic spirometry

JANA KIVASTIK

TARTU UNIVERSITY

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D epartm ent o f Physiology, U niversity o f Tartu, Tartu, Estonia

D issertation is accepted for the com m encem ent o f the degree o f D octor of M edical Sciences on M arch 15, 2000 by the D octoral C om m ittee o f M edical Sciences, U niversity o f T artu, E stonia

O pponent: P rofessor E sko L änsim ies, M .D ., Ph.D . D epartm ent o f C lini

cal Physiology and N uclear M edicine, U niversity o f Kuopio, F inland

C om m encem ent: M ay 3, 2000

P ublication o f this dissertation is granted by the Faculty o f M edicine, University o f T artu

Tellim us nr. 212

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LIST OF ORIGINAL PUBLICATIONS

The thesis is based on the follow ing original publications and on som e unpub

lished data:

I J. Kivastik, P.-H. K ingisepp L ung function in Estonian children: effect o f sitting height. Clin P hysiol 1995; 15: 2 8 7 -2 9 6 .

I I J. Kivastik, P.-H. K ingisepp D ifferences in lung function and chest dim en

sions in school-age girls and boys. Clin P hysiol 1997; 17: 1 4 9 -15 7.

I I I J. Kivastik, P.-H. K ingisepp Flow -volum e loop param eters in healthy ch il

dren and in children with respiratory sym ptom s. Eesti A rst 1999; 4: 291 — 294 (in Estonian).

IV J. K ivastik R eview : Paediatric reference values for spirom etry. Clin P hysiol 1998; 18: 4 8 9 -4 9 7 .

A rticles are reprinted with perm ission o f copyright owners.

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ABBREVIATIONS

A - age,

ATS

— A m erican Thoracic Society,

BiacrD

— biacrom ial diam eter,

ERS

— E uropean R espiratory Society,

F E F25, F E F50, F E F75 — forced expiratory flows, when 25% , 50% and 75% of forced vital capacity has been exhaled,

FEF25-75 (or M M E F ) — m ean forced expiratory flow during the m iddle h alf o f the forced vital capacity (or m axim al m id-expiratory flow ),

F E V i — forced expiratory volum e in one second, F V C — forced vital capacity,

H — standing height,

P E F — peak expiratory flow,

R2

— coefficient o f determ ination,

RSD

— residual standard deviation,

S H - sitting height,

S R — standardised residual,

ThD

— thoracic depth,

ThW

— thoracic width,

TLC

- total lung capacity,

V C — vital capacity.

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1. INTRODUCTION

“When you can’t breathe, nothing else matters”

(A trademark of the American Lung Association) A sthm a is a com m on disease in all parts o f the world, and establishing the diag

nosis is as im portant to clinical practitioners as it is to epidem iologists. A sthm a has always been a clinical diagnosis based on a characteristic pattern of sym p

toms. The last decade, how ever, has seen increasing recognition o f the im por

tance o f objective pulm onary function m easurem ents in the clinical m anage

m ent o f adult and paediatric asthm a (K lein et al., 1995; Taylor, 1997; N ational A sthm a Education and Prevention Program , 1997). In practical term s, the diag

nosis o f asthm a ought to rely on a careful history follow ed by spirom etry in all cases.

Pulm onary function tests are useful for a num ber of reasons. They enable us to objectively follow the course o f respiratory disease processes and to docu

m ent the im pact o f both acute and long-term therapeutic interventions on those processes; to m onitor the effects o f environm ental and occupational exposures and to assess the general condition o f the child (Q uanjer et al., 1989; C astile,

1998).

The interpretation o f results of lung function tests usually relies on com pari

son with reference or predicted values derived from a “norm al” population. For physiologists, “norm al” is the m ost representative o f its class and reveals the sm allest deviations from the average (Polgar, 1990). In norm al children and adolescents the increase o f height, as they grow older, is expected to go along with the corresponding developm ent o f pulm onary function. That is the reason why the age and height variables are considered good predictors o f pulm onary function.

Several sets o f reference values have been published over the last decades and “norm ality” for a given age and height varies considerably across these data. Furtherm ore, as for other anthropom etric m easures, such as height, birth cohort effects have been described — that is, m ean values within each age group increased over tim e. C ohort effects should be considered a m ajor argu

m ent for updating reference values on a regular basis; otherw ise norm al values gradually lose their sensitivity in the detection o f abnorm al conditions am ong younger cohorts.

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2. REVIEW OF LITERATURE

2.1. History of lung function measurements

The need for fresh air w as recognised in the second century by Galen who be

lieved it reacted with the blood in the left heart and arteries to produce the “vital spirit” . H arvey (1 5 7 8 -1 6 5 7 ) dem onstrated the circulation o f the blood through the lung and M alpighi (1 6 2 8 -1 6 9 4 ) show ed the proxim ity of the capillaries to the sm allest air spaces, w hich paved the way for a better understanding of lung function (C otes, 1993).

The m easurem ent of the air volum e, which a hum an can inhale or exhale, was put on a quantitative basis two hundred years later in a report to the Royal M edical and C hirurgical Society. John H utchinson, a London surgeon, had de

signed a spirom eter for his research, and one o f the outcom e m easurem ents he used was the “vital capacity” as “the greatest voluntary expiration follow ing the deepest inspiration” (H utchinson, 1846). In spirom eter the m ovem ent o f air to or from the lung causes changes in the position of a carefully balanced cylindri

cal bell, w hich leads to the recording of the volum e changes on a volum e- calibrated m oving chart. H utchinson studied m ore than two thousand men and show ed that the vital capacity (VC) is related to the height, the VC in adults d e

creases with age and is reduced by excess w eight and by lung disease. The first studies o f V C in norm al children w ere conducted by Em erson and Green in

1921, and by Stew art in 1922 (D ickm an et al., 1971).

It becam e apparent that vital capacity m easurem ents did not fully evaluate ventilatory function. Early attem pts to study dynam ic aspects o f ventilation failed m ainly because the available tools were not sufficiently sensitive to fol

low instantaneous respiratory m ovem ents. A m ore accurate evaluation of the dynam ic behaviour o f the respiratory system becam e possible only after the de

scription of the pneum otachograph (Fleisch, 1925). In 1933 H erm annsen was the first to record the sub ject’s ability to hyperventilate m axim ally over a short tim e interval. A fter his description, which has rem ained a landm ark in the de

velopm ent o f clinical respiratory physiology, several investigators started to relate the sensation o f dyspnoea to the m axim um breathing capacity (Y em ault,

1997).

French scientists tried to find a substitute for the m axim um breathing capac

ity, w hich they disliked because o f the follow ing reasons: the directly m easured m axim al ventilation is tiring and cannot be repeated m ore than three to five tim es during the sam e session, it is difficult to m easure correctly, and it needs a certain degree o f training. T he use o f the proportion of the vital capacity which could be expired in one second (“capacite p ulm onaire utilisable q I ’effort” , the

“pulm onary capacity usable on exercise”) as a guide to airw ays obstruction was introduced by T iffeneau in 1947. D espite the brilliant observations, the contri

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bution o f French scientists rem ained ignored for a tim e by other countries. Only in 1957 the B ritish T horacic Society adopted recom m endations concerning the term inology of the m easurem ent of ventilatory capacity. The term “tim ed V C ” was replaced by the expression “forced expiratory volum e over a stated interval of tim e” and hence FEV j (Y em ault, 1997).

In 1955 F ow ler and colleagues, using pneum otachogram s, provided evidence that the acceleration o f the flow rate during the first several tenths o f a second was so high that an accurate recording o f this portion o f the trace with a spi

rom eter was considered uncertain. Therefore, they advocated m easurem ent o f the average flow over the m iddle o f a rapid m axim al expiration — this is how the m axim al m id-expiratory flow (M M EF or F E F25_75) was bom (Y em ault,

1997). The replotting o f events during a forced expiration as flow against vol

ume (H yatt et al., 1958), instead o f volum e against time, resulted in the flow- volum e curve (Figure 1).

Time (seconds) Volume (L)

Figure 1. Two possibilities to record forced expiration. A. Volume recorded as a func

tion of time, the spirogram. FEVb forced expiratory volume in 1 second. FEF25_75, mean forced expiratory flow during the middle 50% of the forced vital capacity (FVC).

B. Flow recorded as a function of volume, the flow-volume curve. FEF25, FEF50, FEF75, forced expiratory flows when 25, 50 or 75% of FVC has been exhaled. (From Hyatt et al., Interpretation o f pulmonary function tests: a practical guide. Philadelphia, Lippin- cott-Raven Publ. 1997).

The pulm onary function testing has w itnessed m any advances over the last three decades. The m ajority o f these advances involve autom atization of routine lung function m easurem ents. The m arketing o f low -cost com m ercial spirom eters and know ledge that spirom etry is m ore sensitive than the clinical assessm ent o f flow abnorm alities has m ade the technology for these m easurem ents widely avail

able. The diffusing capacity test and body plethysm ography have also becom e routine tests in lung function laboratories.

There are also m any new techniques that are applicable prim arily in the re

search setting. If the standard reporting procedures are firm ly established, if large population studies are com pleted show ing the range o f norm al and the

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patterns of abnorm ality with disease — m aybe then new m ethods like the use of the negative expiratory pressure technique to detect expiratory flow lim itation, the forced oscillation technique to assess airw ay resistance, or the use o f expired nitric oxide and carbon m onoxide in the assessm ent o f airw ay inflam m ation will be available for w ider clinical application (Johnson et a l , 1999).

In E stonia, pulm onary function studies began in the years 1 92 6-1932, when A lfred Fleish was a professor o f physiology at the U niversity o f Tartu and used his pneum otachograph for research. M easurem ents of lung volum es and capaci

ties by a w ater sealed spirograph in children resulted in presenting norm al val

ues (V asar and Laidre, 1974; S illa and Teoste, 1989). No extensive studies reg

istering the flow -volum e loop in children have been carried out in Estonia.

2.2. Lung function from infancy through adulthood 2.2.1. Lung development and growth

A t birth, the lung begins the function for which it was prim arily designed during the prenatal developm ent — gas exchange. The discontinuity provoked by the rem oval o f lung w ater and its replacem ent by air and by the onset of respiration is, how ever, m ore a functional rather than a structural character. Lung develop

m ent is indeed a continuous process that begins around the 26!h day o f gestation and lasts into postnatal life (Thurlbeck, 1982; Burri, 1997). In theory, norm al lung grow th starts w hen lung developm ent is com pleted, but there is evidently no way to delineate this transition. T herefore, lung developm ent blends im per

ceptibly into grow th, and the latter blends into ageing (Burri, 1997).

The lung appears around the 26th day o f gestation as a ventral diverticulum o f the foregut. T he epithelial tubule divides rapidly and the tubular tree pre

form s, through grow th and branching, all the conductive airw ays down to their last generations by the 16th or 17th w eek of gestation. Thereafter, all airways from the bronchus to the term inal bronchiole increase linearly in diam eter. This continues after birth — airw ays increase in diam eter and length by two to three tim es betw een birth and adulthood (Jeffery, 1995).

True alveoli do not begin to develop until about 28th to 34th weeks o f gesta

tion and increase rapidly in num ber, size, and com plexity (Farrell, 1982; Fisher et a l , 1990; B urri, 1997). The exponential grow th o f alveolar num bers has been generally accepted, although large variations betw een the estim ated num bers at birth and at the end o f m aturation still exist. This is probably partly so because of large individual differences. The num ber at term varies: about one-third to one-half o f the adult num ber (Jeffery and Hislop, 1995), or 1 5 -2 0 % of the adult num ber (Langston et a l , 1984). T he earlier idea o f reaching a plateau in the num ber o f alveoli at approxim ately 8 years o f age (D unnill, 1962) was chal

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lenged in favour o f the concept of a slow but continuously increasing num ber through adolescence (Em ery and W ilcock, 1966). Som e authors have stated later that alveolization m ight be com pleted within 1 2 -2 4 m onths and w ould not last longer, except at a very reduced pace (Thurlbeck, 1982; Z eltner and Burri, 1987). From the practical point of view, these concepts put regenerative and corrective adaptations to an injury sustained at different ages into a different light. F urther grow th in lung volum e occurs by an increase in alveolar diam eter, resulting in the doubling o f lung volum e betw een the ages o f 8 and 25. It is gen

erally thought that the num ber o f alveoli in an adult is 300 m illion (D unnill, 1962; Farrell, 1982), but the final num ber may depend upon body length and may vary from 212 m illion to as high as 605 m illion (A ngus and Thurlbeck, 1972).

C hanges in the dim ensions and num bers o f the com ponents o f the respiratory tract are associated w ith concom itant changes in pulm onary function, especially in lung volum es. W hen the infant or young child is com pared with the adult, how ever, certain param eters of pulm onary function rem ain unchanged if they are related to a standard reference, such as height or body surface area (T a

ble 1).

Table 1. Comparison of lung function in the newborn and adult*

Newborn Adult

Body weight, kg 3 70

Body surface area, m2 0.21 1.70

Lung surface area, m2 2.8 64-75

Lung surface area, m2/kg =1 =1

Tidal volume, ml 20 490

Tidal volume, ml/kg 7 7

Alveolar ventilation, ml/min 400 4200

Alveolar ventilation, ml/m2/min 2.3 2.3

* From Fisher et al. Pulmonary function from infancy through adolescence. In: Scarpelli EM. Pulmonary physiology: fetus, newborn, child and adolescent. 2nd ed. Philadelphia, Lea & Febiger, 1990; 421-445.

The description o f lung function throughout life is not easy to com plete. B e

cause o f difficulties in studying lung function in infants and young children (will be discussed in section 2.4.), it is possible that m any patterns o f physiol

ogic developm ent from the neonatal to school age will have to be established by forw ard or backw ard extrapolation o f relatively few reliable data (Polgar and W eng, 1979). T he recent developm ent o f m easuring techniques for infants and small children and for older people will probably allow the com pletion o f stud

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ies with the description o f lung function changes from birth to senescence. So far several studies have focused on changes in pulm onary function from the pre

school to the old ages, but the transitions betw een the early grow th phase, m atu

ration phase, young adult plateau, and the decline phase, have not been defined fully as yet (Polgar, 1990).

The data from subjects aged betw een 8 and 90 show ed that FVC and FEVj increased up to the age o f 20 in wom en and up to the age o f 27 in men, and then started to decrease, tw o separate linear regression lines w ere derived for both genders (K nudson et a l , 1976). T he other group described the developm ent of spirom etric variables by a num ber o f linear m odels for several age intervals with intervening “breakpoints” (Figure 2). In their data FV C and FEVi of males increased slow ly with age until the age o f 12, and then increased rapidly until the age o f 17 (FEVO or 18 (FV C ), and continued to grow slow ly until the onset o f the decline at age 26. In fem ales, the increased grow th rate occurred earlier (age 1 0 -1 6 years) and was less pronounced than in m ales. A fter that, FEV | continued to grow slow ly until age 27 years, w hereas FVC started to decline at age 17 years (Sherill et a l , 1992).

Figure 2. Predicted lung function curves for healthy subjects of an average height. Fe

males are plotted using solid lines, males with dotted lines. Abbreviations as in Figure 1. Vmax50 is the same as FEF50(From Sherrill et al. Continuous longitudinal regression equations for pulmonary function measures. Eur Respir J 1992; 5: 452-462).

One research team studied subjects aged 8 -8 0 years and used piecew ise poly

nom ials with a single change point (2 0 years for m ales and 18 years for fe

m ales) in the reference equations (H ankinson et a l , 1999). O thers have found 14

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that grow th o f the airw ays and increase of the size o f the alveoli continues in fem ales until the height ceases to increase with age, but continues at a slow er pace in m ales till the mid 20s, attributed to the m uscularity effect (Schrader et a l, 1988; H ibbert et a l, 1995).

T he literature suggests that using only two equations, one for children and young adults and the other fo r older subjects, cannot adequately account for m aturation as it interacts with grow th and ignores an apparent period in the late teens, 20s, and early 30s in which pulm onary function appears relatively stable (B urrow s et a l, 1983). This is in agreem ent with the paper by K ristufek et al.

(1987) assum ing that process of grow th, m aturation, and ageing are uninter

rupted, and therefore they selected a single equation to cover the age range 6 -8 1 years. In their data VC and FEV] increased up to 18 years in fem ales and up to 21 years in m ales, after w hich they rem ained approxim ately constant up to 33 and 36 years respectively, then a physiological decline was observed.

2.2.2. Effects of gender and race

G ender differences in anatom ic lung grow th have been described well enough.

The lungs o f boys aged 6 weeks to 14 years were larger than those o f girls o f the sam e height. This was explained by more (but not larger) alveoli present in male lungs, and these differences were attributed to m ale sex horm ones (T hurl

beck, 1982).

Several authors have reported increased flow s and reduced resistance in the girls suggesting that the airw ay function is dim inished in boys com pared with girls during both infancy and childhood (Zapletal et a l, 1987; R ona and Chinn, 1993; H ibbert et a l , 1995; M erkus et a l , 1996; Stocks et a l, 1997; B ecklake and K auffm ann, 1999). This can m ainly be explained by differences in airw ay size, which im plies that for the sam e lung volum e, girls have larger airw ays than boys do. T his may contribute to the higher prevalence o f asthm a and w heezing reported in boys com pared with girls at all ages up to puberty (W eiss et a l , 1992; G old et a l , 1994; H ibbert et a l , 1995).

To explain the m arked variability o f m axim al expiratory flow rates betw een individuals with lungs o f com parable volum e, the term “dysanapsis” was p ro

posed to describe w hat appeared to be this w eak link betw een airw ay and lung size (G reen et a l , 1974). This was attributed to disproportionate grow th b e

tween the airw ays and the air spaces. A recent review o f gender differences in lung function has stated that both in men and wom en, the grow th o f the lung parenchym a and its airw ays occurs independently, and that the configuration of the adult fem ale lung is the result o f proportional grow th o f its airw ays in rela

tion to its parenchym a. H ow ever, the adult m ale lung is the result o f dysanaptic growth — that is, grow th o f the airw ays has lagged behind in com parison with the lung parenchym a (B ecklake and K auffm ann, 1999).

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M en and w om en also differ as to the age when they reach the m axim al val

ues of lung function indices, as was described in section 2.2.1. Fem ales appear to reach their m axim al values earlier, at approxim ately age 16 to 18, w hereas m ale lung volum es and flow s usually continue to increase after the cessation of grow th in height to age 25 or more. O ne possible reason is that m uscle mass grow s during the puberty, stim ulated by androgens. Thus, m uscle grow th in m ales is m uch greater than in fem ales, and it continues beyond puberty in m ales, reaching a m axim um at around age 25, especially with training (Schrader et a l, 1988; L ebow itz and Sherrill, 1995; M erkus et a l, 1996).

Race has been consistently show n to be an im portant determ inant o f lung func

tion. W hen com pared with C aucasians, m ost other races usually show sm aller lung volum es and low er forced expiratory flow s (N eukirch et a l, 1988; R ahm an et a l , 1990; C hinn and Rona, 1992; Jacobs et a l, 1992; Roizin et a l, 1993;

Azizi and H enry, 1994; C onnett et a l, 1994; H ankinson et a l, 1999). The rea

son for these differences is yet unclear. They may be related to the body pro

portions and in particular to a sm aller ratio o f sitting to standing height charac

teristic o f the racial groups studied (Hsi et a l , 1983; A sher et a l , 1987; C onnett et a l , 1994). A part from discrepancies betw een races, also slight differences may exist betw een ethnic groups within the sam e race. There is abundant m ate

rial o f m easurem ent on different groups o f C aucasians living in various coun

tries on various continents. H ow ever, as the confidence limits are too broad for any group, it is difficult to find any real differences betw een ethnic groups by com paring the m easurem ents o f different investigators. Ethnic differences in chest w all dim ensions (R ahm an et a l , 1990), environm ental differences and socioeconom ic factors, racial differences in lung grow th and m aturation, differ

ent heights and ages when pubertal changes start (C onnett et a l , 1994), lan

guage and im m igrant status (Polgar and W eng, 1979) — all these factors are also thought to be im portant in determ ining the lung function o f ethnic groups.

2.2.3. Factors modifying lung development and growth

L ung developm ent and grow th may be influenced by several m odulating fac

tors, w hich can lead to an im paired lung function in o n e’s later life. One concept that explains this association is “program m ing” — the perm anent alterations of the structure and function o f organs and tissues by factors during sensitive peri

ods o f rapid grow th may change the function and developm ent o f specific dis

eases later in life. F actors im plicated in “program m ing” of the respiratory sys

tem may be fetal nutrition, fetal exposure to m aternal sm oking during preg

nancy, and exposure to environm ental allergens or viral respiratory infections during infancy. A dverse influences during this period o f grow th may operate by dim inishing airw ay or alveolar grow th and hence the m axim al lung and airw ay size attained, by increasing airw ay responsiveness to allergens, viruses and air

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pollutants in later childhood or adult life, by im pairing collagen and elastin de

velopm ent in the lung parenchym a with secondary effects on the airw ay func

tion, or by som e com bination o f all three. Finally, the age-related decline in res

piratory function w hich com m ences in mid adult life m ay be m ore rapid or reach a critical threshold at an earlier age in those persons who did not achieve their m axim al fetal and early childhood growth potential (D ezateux and Stocks,

1997).

C onflicting data have been reported on the effect o f intrauterine grow th reta r

dation on lung volum es in children. O ne study reported that FVC was decreased after adjustm ent for the gestational age, parental sm oking, and social factors (R ona et a!., 1993), others found that lung volum es were norm al, but expiratory flow values were reduced in children of low birthw eight (C han et al., 1989;

N ikolajev et al., 1998). Small sam ple sizes and exclusion o f preterm infants and those with perinatal problem s have precluded a detailed exam ination of hy

potheses regarding fetal nutrition. Individualised birth centiles and im proved m ethods for the assessm ent of intrauterine grow th retardation are required if the extent o f the latter is to be recognised and its effects assessed (D ezateux and Stocks. 1997).

Reduced forced expiratory flow s have been identified in school-age children in whom pneum onia, bronchitis, and other low er respiratory tract illnesses have been docum ented prospectively (Pistelli et al., 1992; W eiss et a l, 1992; Bors- boom et a l, 1993; R ona and C hinn, 1993; M ostgaard et a l, 1997; D roste et a l, 1999). H ow ever, these data do not resolve the question o f w hether reduced ex piratory flow precedes or follow s the initial episode o f illness in o n e’s early childhood. The follow -up studies of infants in w hom lung function tests were perform ed before any illness developed show ed that the initial lung function was low er in infants who later developed low er respiratory tract illnesses, sug

gesting that a pre-existing developm ental condition of the lung may be involved in the pathogenesis of these illnesses (M artinez et a l, 1988; T ager et al., 1993;

D ezateux et a l, 1999).

Exposure to m any environm ental and social influences during fetal and early postnatal life continues throughout later childhood and adult life and the poten

tially adverse effects o f earlier exposures may be difficult to distinguish from the later ones (D ezateux and Stocks, 1997). P assive sm oking w ould be a typical example.

Fetal exposure to m aternal sm oking during pregnancy has been clearly dem onstrated to be associated with increased health problem s in infants and older children, including increased rates of w heeze-associated low er respiratory ill

ness and pneum onia (ATS. C igarette sm oking and health, 1996; M organ and M artinez, 1998). M aternal sm oking seems to m odify lung developm ent so that the infant will have a dim inished low er airw ay function and, as a result, has an increased risk o f developing w heezing upon a viral infection o f the bronchial

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tree (D ezateux and Stocks, 1997). The im pact o f m aternal sm oking on w heezing illness m ay dim inish later in childhood. It could be explained by the fact that the grow th of the airw ays m akes geom etry of the small airw ays less relevant in producing sym ptom s after the pre-school years. In other w ords, children with early, transient w heezing grow out o f their predisposition to w heeze unless they have developed true asthm a (M artinez et al., 1995).

One difficulty in determ ining the tim ing of the im pact o f m aternal sm oking on the infant lung function has been that m ost m easurem ents have been con

ducted in early infancy after a relevant period of postnatal, passive exposure to m aternal sm oking. T his has m ade it difficult to know if the im pact of m aternal sm oking was truly an in utero one or was it due to postnatal exposure. Several studies suggest that the negative im pact is substantially prenatal in its tim ing (M artinez et al., 1995; M organ and M artinez, 1998; G illiland et a l., 2000). A study o f 108 preterm infants prior to discharging them from hospital (no post

natal exposure to tobacco sm oke), provided confirm atory evidence that these in utero effects on lung function are evident prior to the m iddle o f the third tri

m ester; indeed, prior to any significant effect o f sm oking on the overall w ell

being as assessed by birthw eight (H oo et a l., 1998). A nother research team car

ried out lung function tests w ithin 72 hours o f delivery and found that m aternal sm oking was associated w ith a significant reduction in birthw eight and length, also with a reduction in static com pliance in boys and conductance in girls, but no reduction in lung volum e was observed when related to w eight (M ilner et al., 1999). A dverse effects o f antenatal m aternal sm oking represent a good reason to develop intervention strategies to prevent the acquisition o f the sm oking habit in adolescents and to aid pregnant wom en in effective sm oking cessation as soon as possible in pregnancy (ATS. C igarette sm oking and health, 1996).

Postnatal exposure of children to sm oke also seems to have som e effect, as sm oking by household m em bers is associated with som e increase in respiratory sym ptom s and decrease in forced expiratory flows (B urchfiel et al., 1986; Rona and C hinn, 1993; Haby et al., 1994; C uijpers et al., 1995; C unningham et al., 1996; C ook et al., 1998; B urr et al., 1999). A m ongst older children, there may be found already som e active sm okin g, which is associated with evidence of m ild obstruction and slow ed grow th of lung function in non-asthm atic adoles

cents (G old et al., 1996; B urr et al., 1999). Furtherm ore, the m ain effects of cigarette sm oking on lung function will show in adulthood — current sm okers have a low er F E V b a shortening o f the plateau phase o f the FE V | level that generally occurs betw een 20 and 30 years o f age, and an accelerated decline in FEVi after that w hen com pared to those who form erly or never sm oked (Ulrik,

1999). All these associations show a dose-response relationship. A faster-than- expected annual fall in FEV i is the m ost useful finding in identifying sm okers who are likely to develop severe pulm onary im pairm ent (ATS. C igarette sm oking and health, 1996).

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Studies o f the effects o f training on lung volum es have been perform ed since the early 1960s. S w im m ing has been studied m ost extensively and appears to be the only sport associated w ith a m arked increase in lung volum es and m axim al ex piratory flow s (G aultier and C rapo, 1997). H ow ever, it is unclear w hether the superior lung function found in sw im m ers is due to genetic influences or the result o f training. Som e research groups have found that the sw im m ers had the highest lung volum es already before the training had begun, on the other hand, the num ber o f years o f sw im m ing and/or the earlier age at w hich training begins seems to have a significant bearing on the subsequent lung function (D oherty and D im itriou, 1997). No study has m easured alveolar distensibility in child swim m ers, but norm al distensibility was reported in young adult sw im m ers, suggesting that their large lungs could be achieved by an increase in alveolar num ber, rather than by enlarged alveoli (A rm our et al., 1993).

D iet is a relatively new area o f interest in the field o f pulm onary function. A possible reason seem s to be that the m ost com m on fatal diseases o f the respira

tory system — lung cancer and chronic obstructive pulm onary disease — are so clearly related to tobacco sm oking that other factors have caught little attention (Sridhar, 1995). Interest in vitam in С arose out o f a b elief that accelerated d e

cline in pulm onary function in sm okers m ight be due to deficiencies o f proteo

lytic enzym es, this raised the possibility that antioxidant vitam ins m ight be protective factors in the respiratory system (B ritton et al., 1995; G rievink et al.,

1998). Several studies have shown that frequent fresh fruit consum ption is asso

ciated with higher lung function in both children (C ook et al., 1997) and adults (Strachan et al., 1991; C arey et al., 1998; G rievink et al., 1998; T abak et al., 1999; B utland et al., 2000). There is also som e evidence that the response o f the airw ays to histam ine correlates with the intake o f sodium (B urney et al., 1986) and that the dietary intake o f m agnesium has been show n to have an independ

ent, beneficial influence on lung function and w heezing (B ritton et al., 1994).

2.3. Anthropometric parameters and lung function

The developm ent of lung volum es and flow s in children is highly correlated with an increase in standing height, probably the m ost widely used anthropo

metric index in paediatrics. Therefore, m ost o f the published reference values o f lung function are based on standing height.

D uring puberty (see the next section) and different races reveal different body proportions (ratio o f sitting height to standing height). The use of sitting height (SH) as the indicator o f trunk size in the prediction equations for lung param e

ters would be m ore exact because trunk developm ent m ight be m ore closely

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associated to lung developm ent (Hsi et «/.,1983; S chrader et al., 1984; De- G roodt et al., 1986; A sher et al., 1987; C onnett et al., 1994).

In m am m als, a proportional relationship has been established between body mass, lung volum es, and ventilatory function (Fisher et al., 1990). On this basis body m ass seems to be a plausible independent variable in the prediction equa

tion, but this is fraught with hidden dangers. A bnorm al situations like sickness or unhealthy eating habits can easily disturb the relation between body m ass and lung function (D eG roodt et al., 1986).

Body m ass is the sum o f its constituents, which include body m uscle and fat.

The m uscle com ponent can influence the m axim al respiratory pressures and, hence, all indices of which inspiratory capacity forms a part, and peak expira

tory flow. The fat com ponent can influence the total lung capacity (TLC) and its subdivisions, the w ork o f breathing and, in some circum stances, the airw ay calibre (C otes, 1993). In cross-sectional studies an atypical body m ass can re

flect an excess or dim inution in either fat or m uscle, or both. The effects of these variables on lung function have opposite signs, hence they tend to cancel out each other. Therefore, the overall contribution of body m ass to cross- sectional descriptions o f ventilatory capacity is relatively small. W eight may also be abnorm al for given heights in those with diseases for whom the refer

ence equations are prim arily developed (Lebow itz and Sherrill, 1995).

The effects o f obesity on pulm onary function have been extensively investi

gated in adults, as body mass usually increases from youth to the m iddle age and then dim inishes, som e o f the age-related decline in lung function could be due to the associated changes in body m ass (Cotes, 1993; Q uanjer et al., 1993;

Chinn et al., 1996). M en tend to deposit fat centrally, whilst in wom en the deposition is often peripheral, the effect of w eight gain on lung function has therefore been show n to be greater in men (Chen et al., 1993). Few er studies have addressed the problem o f obesity in children. In children with 147-300%

ideal body w eight, reductions in diffusing capacity, ventilatory m uscle endur

ance, expiratory reserve volum e, FEVi and F E F25..75 have been found (Inselman et al., 1993). C hildren show ed sim ilar sex differences o f fat distribution patterns as adults — there was a positive correlation between lung function and body m ass index in norm al boys and girls, and in overw eight girls, but a negative co r

relation in overw eight boys (Fung et al., 1990).

Standing height m ay be unobtainable in som e patients referred for pulm onary function testing, ow ing to inability to stand or difficulties in m easuring because of thoracic cage deform ity. The m ost conventional m ethod in these cases is the m easurem ent o f arm span and the subsequent estim ation of height using a fixed arm span to height ratio or specific regression equations with arm span (H ibbert et al., 1988; Parker et a l, 1996; A ggarw al et al., 1999).

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2.4. Problems in paediatric lung function testing

Lack of cooperation and coordination lim its the application o f routine proce

dures, such as peak flow m easurem ent and spirom etry in children below 5 - 6 years o f age. H ow ever, a w ide variety o f m ethods has now been developed for use both in ventilated and spontaneously breathing infants. E quipm ent for assessing respiratory function in small children has to be specially m odified to m inim ise dead space and resistance, to m eet safety requirem ents, and to achieve satisfactory sensitivity and frequency response in the presence o f rapid respiratory rates and relatively low signal / noise ratios. A pplication of these techniques requires further evaluation and standardisation, and nevertheless, the assessm ent of lung function in infants and young children w ill probably rem ain far m ore tim e-consum ing than in adults (ATS / ERS statem ent. R espiratory m echanics in infants, 1993)

W hile considerable attention has been paid to the designing reliable pulm o

nary function tests in infants, children aged 3 to 5 years rem ain w ithout reliable and reproducible objective m easures o f their pulm onary function (K anengiser and Dozor, 1994; C astile, 1998). The children o f that age can rarely generate spirom etry test results that m eet ATS and ERS acceptability standards set for adults, m ainly because o f the total tim e o f forced exhalation being shorter than one second in sm aller children. P roducing FEVi rem ains an age-dependent function that may im prove with training. U sing FE V 0.s or FE V0.75 instead sug

gested by som e researchers (Q uanjer et a l, 1989; C otes, 1993; K oillinen et a l, 1998) have not gained w ide acceptance. Im pedance m easurem ents by the im pulse oscillation technique and respiratory resistance m easurem ents by the in

terrupter technique, both perform ed during norm al tidal breathing and requiring only passive cooperation from the child, have been recom m ended for use in children 3 to 6 years old (B isgaard and Klug, 1995).

Perform ing spirom etry with sm all children needs a skilled technician who can explain and dem onstrate the test and answ er the questions, as this can sig

nificantly im prove initial perform ance (C astile, 1998). Especially younger ch il

dren are likely to need training in pre-test sessions in the perform ance o f lung function tests, and doing so while the child is well can provide valuable coop

eration and inform ation later when he or she is ill (M ueller and Eigen, 1994;

Studnicka et a l , 1998). It is often recom m ended to ask the child to “try to blow out the candles on a birthday cake and continue blow ing until the technician tells you to stop” as a better explanation o f forced exhalation (C astile, 1998).

Some authors have reported that directly visualised flow -volum e curves w ere helpful, but others have found them distracting to young children. Som etim es burning candles or changing lights on the screen have been recom m ended (K anengiser and D ozor, 1994).

D uring recent years the potential effects of puberty on lung grow th have been studied. The finding that no single linear or pow er curvilinear relationship

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describes correctly the relationship betw een forced ventilatory m anoeuvres and height throughout childhood was first noted by D ickm an et a l (1971). Sudden changes both in standing height and lung function take place during the adoles

cent grow th spurt, but the lung grow th appears to lag behind the increase in standing height (D eG roodt et al., 1986; Jaeger-D enavit and A lphonse, 1990;

W ang et al., 1993; B orsboom et al., 1993 and 1996; L ebow itz and Sherrill, 1995). It is possible that the use o f sitting height in predicting lung function in adolescents w ould be m ore appropriate than using standing height, because adolescent spurts in lung and trunk grow th could be closer in tim e (Schrader et al., 1984; D eG roodt et al., 1986).

T here appears also to be an elem ent o f “m aturation” during adolescence, w hich is not totally explained by grow th, and it is reflected in the high positive age effects for m ale subjects betw een the ages o f 12 to 13 years through age 18 or 19. S im ilar high age effects are seen in girls starting at age 11 or 12 and ending at 15 to 16 years o f age (B urrow s et al., 1983).

It is m ore likely that the true grow th pattern before and after puberty is more accurately represented by m ultiple equations and discontinuous regression lines, but then care should be taken to avoid abrupt changes in the predicted values from one line to the other (Q uanjer et al., 1989). F or exam ple, correction factors for pubertal stages can be used (R osenthal et al., 1993).

2.5. Reference values for children

In a book published in 1971 P olgar and Prom adhat attem pted for the first time to present all the available inform ation on pulm onary function testing in chil

dren. The anatom ic and functional grow th o f the respiratory system was m en

tioned as the fundam ental reason for the necessity to present data on grow ing children with a dynam ic approach, as opposed to m uch sim pler ways for adults.

T he collection of these data resulted in calculated “sum m ary curves” for each variable, w hich could be used as average prediction standards (Polgar and P ro

m adhat, 1971).

M ore recently, about 50 publications from 1950 to 1986 were com piled in one report (Q uanjer et al., 1989) and several num bers o f papers offering refer

ence values have published after that. R egardless o f the efforts in the standardi

sation o f pulm onary function testing in the last decade, there are still large dis

crepancies betw een different predictions, either for adults or for children. F ac

tors contributing to these differences include sam ple selection, population dem ographics, inclusion o f current or past sm okers, inadequately docum ented potential for occupational exposure and variation in equipm ent, techniques, and com putational m ethods (G lindm eyer et a l, 1995).

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To define a “norm al” population from w hich reference standards can be de

rived, it is useful to adopt the recom m endations on defining a “healthy” child (Taussig et al., 1980):

1) no present acute and no past or present chronic disease o f the respiratory system,

2) no m ajor respiratory disease such as congenital anom alies, destructive type o f pneum onia, or thoracic surgery in the past m edical history,

3) no system ic disease w hich directly or indirectly is know n to influence the respiratory system and general state o f health,

4) no m ore than incidental sm oking experience,

5) no history o f an upper respiratory tract infection during the previous three weeks.

M ost authors o f reference equations have used these or sim ilar inclusion criteria for their reference population, som e have fixed also the conditions o f the surrounding environm ent (K ristufek et al., 1987). O ne research group included all children, and suggested that, when the subjects had not had any m ajor tho

racic, neurological and system ic diseases, then farth er selection on the basis of reported respiratory sym ptom s seem s to have only m inor effects on lung vol

umes, but flow s can be m ore affected (Pistelli et al., 1992). Therefore, the m inim al num ber, severity and nature of trivial respiratory disease episodes that would still allow an individual to be counted in reference population studies for a “norm al” pattern of developm ent have to be determ ined (Polgar, 1990).

There is no agreem ent w hat is the best m odel to represent the relationship betw een a lung function index and an independent variable. A part from the pow er function and the exponential function, linear relationships can still be used in situations, w here the age range was sm all or w here the population had been artificially divided into narrow age ranges (Q uanjer et al., 1989).

M ostly, the age 18 is used as the cut-off betw een paediatric and adult pre

dictive equations. One reason is that m ost reference equations for children are based on subjects with a m axim al age of 16 to 18 years. T he age range o f 1 8 -2 0 years tends to be studied quite seldom , they are excluded from studies both on adolescents and adults. R ecom m endations on reference values for ven

tilatory indices assum e that there is no change in ventilatory function betw een the ages 18 to 25 years in cross-sectional studies, so that an age o f 25 years can be used in the regression equations (Q uanjer et al., 1993). M ore studies are needed for this age group because young adults betw een 18 and 25 years o f age could be a heterogeneous group in term s o f pulm onary function grow th. T hat is, some are still grow ing (have not reached the adult level), som e are in the pla

teau phase and som e have already begun to decline (W ang e t al., 1993).

There is a fundam ental difference o f philosophy over the application o f ref

erence equations — the E uropean ideal is for a set o f standardised equations, which w ould be applicable in all laboratories (Q uanjer et al., 1993), w hile the North A m erican view is that each laboratory should choose equations from the literature which best suit to that laboratory (ATS. Lung function testing, 1991).

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R eference values should be chosen from a study based on the sam e tech

niques that will be used and a healthy population sim ilar to the population being tested in that particular laboratory. This requires exam ining the population ch ar

acteristics, such as age range as well as gender and race com position. A fter a reference standard is chosen, a sm all num ber o f healthy children should be tested, and the results should be com pared with the chosen values from the lit

erature (Q uanjer et al., 1989; Pattishall, 1990; Stocks and Q uanjer, 1995). U n

fortunately, it has been show n that reference values were often chosen because they w ere available in the pulm onary function test equipm ent softw are, rather than because they had been analysed and found to be the best for the local population (G hio et al., 1990; Pattishall, 1990).

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3. AIMS OF THE PRESENT STUDY

The m ain objective of this cross-sectional study was to describe the relation

ships betw een anthropom etric param eters and lung function in children throughout the school-age and to find out how the respiratory diseases and sym ptom s m ay change these relationships. A ccordingly, the present study had the follow ing specific aims:

1. To find out w hether the differences in the perform ance o f the lungs o f boys and girls o f the sam e height may be explained by differences in sitting height and thoracic size.

2. To investigate if an im paired lung function could be dem onstrated in sym p

tom atic schoolchildren, even in the absence o f asthm a diagnosis.

3. To com pare lung function test results from healthy non-sm oking schoolchil

dren with different reference values from the literature.

4. To develop reference equations for dynam ic spirom etry for Estonian children and adolescents.

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4. MATERIALS AND METHODS

4.1. Study area and subjects

E stonia is a country near the B altic Sea, with an area o f 45,226 km 2, and the overall population in 1992 was about 1.53 m illion. The ethnic com position in 1992 was as follow s: E stonians approxim ately 60%, R ussians 30%, and others 10%. There w ere 137,133 students in 553 E stonian-language prim ary or secon

dary schools in the academ ic year 1992/93 (M inistry o f Education).

The cross-sectional study was carried out at eight different schools in Estonia from Septem ber 1992 through to April 1995. The schools were chosen from the two biggest tow ns in Estonia (Tallinn with a population of 471,600 and Tartu — 113,400 inhabitants according to “Estonia. A Reference Book, 1993”) and from one county in N orthern Estonia (Loo and Saku Secondary Schools in Harju county) and one in Southern Estonia (A ntsla Secondary School in Võru county).

In each selected school, random sam pling o f classes was used and all chil

dren w ho w ere at school on the day o f exam ination were offered to participate.

1,469 children received questionnaires for their parents.

The study was approved by the Ethics C om m ittee of the U niversity o f Tartu.

4.2. Questionnaires

Each child received a questionnaire concerning respiratory sym ptom s and dis

eases, a m edical history, and drug intake. The questionnaire was com pleted at hom e with the aid o f the ch ild ’s parents. Table 2 lists the questions used in the present analysis.

Table 2. Questions on asthma or respiratory symptoms in the questionnaire (translated from Estonian)

Quest. No.

Q1 Has a doctor ever diagnosed your child as having asthma?

Q2 Has your child had frequent cough (more than three months per year)?

Q3 Has your child had shortness of breath?

Q4 Has your child had wheezing or whistling in the chest?

Q5 Is your child currently receiving any treatment?

Sm oking habits w ere asked directly from the child. The child was considered as a sm oker, if he or she sm oked m ore than one cigarette per week. The school- doctor’s reports w ere also used to find specific diagnoses. The decim al age (ac

curacy to 0.1 years) was calculated from the actual date and date o f birth.

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4.3. Anthropometric measurements

Standing height and body w eight w ere m easured in all subjects w ithout w earing shoes. Standing height was m easured, as the child stood erect, with heels close together and the arm s hanging naturally at the sides. The external auditory m eatus and the low er border o f the orbit w ere in a plane parallel with the floor.

Sitting height was m easured w hile the child was in an upright sitting p osi

tion, from the vertex o f the head to the base of the seat. B oth heights were m easured using the m etal anthropom eter and read to the nearest m illim etre.

W eight in light indoor clothing was m easured using beam platform scales and recorded to the nearest 0.5 kg.

Thoracic dim ensions w ere m easured with a large m etal sliding calliper with the subject standing, at the end o f norm al expiration. T horacic width (ThW , transverse chest diam eter) and depth (ThD , antero-posterior chest diam eter) w ere m easured at the level o f the fourth rib, biacrom ial diam eter (B iacrD ) b e

tw een acrom ions (the lateral ends of scapulas).

4.4. Lung function tests

The spiroanalyser Pneum oscreen II (Erich JA EG ER G m bH, H oechberg, G er

m any) was used to register the static and dynam ic lung param eters. The m eas

urem ent o f flow w as carried out by a pneum otachographical, open system , the volum e was determ ined by electronical, digital integration. The analyser was calibrated with 1 litre syringe each tim e the unit was sw itched on.

D uring the test, three to fou r children w ere w atching the perform ance o f their classm ate in order to reduce the need for instructions before the start o f the test. The child was sitting during the test, a noseclip was used. A fter exhaling as deeply as possible each child was asked to breathe in to total lung capacity, sub

sequently blow out as hard and fast as possible to residual volum e, and then sim ilarly to breathe in back to TLC . The m axim um envelope o f at least three sim ilar flow -volum e loops was analysed. In this study, the follow ing volum es and flows (corrected to body tem perature and pressure, saturated with w ater vapour conditions) w ere exam ined:

* forced vital capacity — FV C,

* forced expiratory volum e in one second — F E V b

* peak expiratory flow — PEF,

* forced expiratory flow s when 25, 50 and 75% o f FV C had been exhaled — F E F25, F E F50and F E F7 5,

* mean forced expiratory flow during the m iddle 50% o f the FVC — FE F25-75.

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4.5. Statistical analysis

D escriptive data w ere treated by univariate analysis. W hen dividing m aterial into the age groups, children in the age range from 5.0 to 5.9 years w ere in

cluded in age group 5 and so on. W hen dividing into height groups, the m aterial was subdivided into 5-cm intervals (Table 3).

Table 3. Height groups Group Height inter

val in cm

Group Height inter

val in cm

Group Height inter

val in cm

Group Height inter

val in cm

1 <120 5 135-139.9 9 155-159.9 13 175-179.9

2 120-124.9 6 140-144.9 10 160-164.9 14 180-184.9

3 125-129.9 7 145-149.9 11 165-169.9 15 185-189.9

4 130-134.9 ⁸ 150-154.9 12 170-174.9 16 >189.9

Inter-group differences for boys and girls w ere assessed for statistical signifi

cance using an unpaired S tuden t’s t-test. The chi-square test was used for test

ing differences in the prevalence o f respiratory sym ptom s betw een boys and girls. The Pearson correlation and partial correlation analyses were used to as

sess relationships betw een lung function and anthropom etric variables.

Stepw ise m ultiple regression analysis was perform ed with lung function pa

ram eters as dependent variables and age, anthropom etric param eters, respiratory sym ptom s, and illnesses as independent variables. Independent variables were included in the m odel if they w ere significant at p<0.05.

W hen com paring our data with reference values from the literature, stan

dardised residuals (SR) w ere calculated for the children from each reference equation as follows:

observed value - predicted value SR — —— ---

RSD

w here R SD is the residual standard deviation from the literature. A s the equ a

tions with the w eakest relation o f standardised residuals to age were preferred, this relationship was tested for each equation in regression m odels with SR as the dependent and age as the independent variable.

Statistical significance was set at 0.05 level. The analyses were m ade using S tatistica for W indow s 5.0 (StatSoft Inc., USA) statistical softw are.

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5. RESULTS

5.1. Main characteristics of the subjects

From 1,469 children w ho w ere offered to participate five children did n ot agree to m ake the tests and nine brought incom pletely answ ered questionnaires.

Finally, the data o f 1,455 children aged 5 -1 8 years w ere obtained and analysed.

G eographical distribution o f children studied is given in Table 4.

Table 4. Distribution of children

Region Number of boys Number of girls Total

Northern Estonia

Tallinn (2 schools) 144 226 370

Loo 40 47 87

Saku 104 80 184

Southern Estonia

Tartu (3 schools) 335 311 646

Antsla 60 108 168

Total 683 772 1,455

The 1,455 study subjects w ere separated by gender, the num ber o f children in age groups is given in Figures 3 and 4. The range o f standing height w as 109 to 185 cm in girls and 106 to 195 cm in boys, and o f w eight 18 to 90 kg and 15 to 96 kg, respectively. C om parison o f basic som atic characteristics w ith recent anthropom etric tables (G rünberg et a l , 1998) show ed th at m ost o f the children studied w ere w ithin the norm al grow th curves for height and w eight for Estonian children, except 12 boys above the 97th pecentile and 6 boys below the 3rd percentile for height, 9 boys above the 97th percentile and 9 boys below the 3rd percentile for w eight, 14 girls above the 97th percentile and 14 girls below the 3rd percentile for height, 5 girls above the 97th percentile and 17 girls below the 3rd percentile for w eight.

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200

Age (years)

Figure 3. Distribution of boys (n=683) by age. Each column represents two age groups.

Figure 4. Distribution of girls (n=772) by age. Each column represents two age groups.

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5.2. Gender differences in lung function and effects of pubertal growth spurt (I, II)

A nonlinear increase in spirom etric indices with increasing height as w ell as age was found (Figures 5 and 6). Plots o f lung function variables according to stature or age show ed a heteroscedastic distribution, i.e. the scatter increased at increased height or age. D ata o f FEV i w ere available for 578 boys and 569 girls because the duration o f forced expiration in som e children, especially the younger ones, w as less than one second.

H eigh t (cm )

Figure 5. Forced vital capacity as a function of standing height in girls (n=772).

W hen plotting the m ean values o f standing height as a function o f age, the growth spurt in standing height, an im portant indicator o f the onset o f puberty, was from 11 to 13 years in girls and from 13 to 15 years in boys (I). M ost lung function param eters underw ent also the biggest changes in these age periods, growth spurts w ere m ore pronounced in boys (Figure 7). Until the age o f

11 years, boys had higher values for FVC and PEF, the differences for F E V b F E F 5o and F E F75 w ere not significant. As the grow th spurt began earlier in girls, at the ages o f 12 and 13 years their flow values w ere higher than in boys o f the same age. T eenage girls never had higher values o f FVC and F E V b A fter the age o f 14 years, FVC, FEV] and PEF w ere m uch higher in boys, w hile differences in values o f FE F50 and FEF75 w ere not found.

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Age (years)

Figure 6. Peak expiratory flow as a function of age in boys (n=683).

11

5 6 7 8 9 10 11 12 13 14 15 16 17 18

Age group (years)

- o - PEF - a - FEF25

FEF50

Figure 7. Mean values of flows by age groups in boys (n= 683).

A s from the age o f 14 years the boys w ere significantly taller than girls, the height should also be considered w hen com paring tw o sexes. Paper II presents m ean values o f different lung function variables as the function o f height. There

relationship with anthropometric indices and respiratory symptoms, reference values for dynamic spirometry

LUNG FUNCTION

IN ESTONIAN SCHOOLCHILDREN:

relationship with anthropometric indices and respiratory symptoms,

reference values for dynamic spirometry

JANA KIVASTIK

64

LUNG FUNCTION

IN ESTONIAN SCHOOLCHILDREN:

relationship with anthropometric indices and respiratory symptoms,

reference values for dynamic spirometry

JANA KIVASTIK

CONTENTS

LIST OF ORIGINAL PUBLICATIONS

ABBREVIATIONS

ATS

BiacrD

ERS

R2

RSD

ThD

ThW

TLC

1. INTRODUCTION

2. REVIEW OF LITERATURE

2.1. History of lung function measurements

2.2. Lung function from infancy through adulthood 2.2.1. Lung development and growth

2.2.2. Effects of gender and race

2.2.3. Factors modifying lung development and growth

2.3. Anthropometric parameters and lung function

2.4. Problems in paediatric lung function testing

2.5. Reference values for children

3. AIMS OF THE PRESENT STUDY

4. MATERIALS AND METHODS

4.1. Study area and subjects

4.2. Questionnaires

4.3. Anthropometric measurements

4.4. Lung function tests

4.5. Statistical analysis

5. RESULTS

5.1. Main characteristics of the subjects

5.2. Gender differences in lung function and effects of pubertal growth spurt (I, II)