Lung function measurements in children - copsac

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prospectively if baseline lung function is lower in infant developing RSV-bronchiolitis. On the other hand comparing bronchial responsiveness showed a narrow confidence interval (-26% to +20%); i.e. suggesting it seems unlikely that bronchial hyperresponsiveness was the distinguishing factor in infants later developing RSV-bronchiolitis. The strengths of this study were the unique prospective nature of the birth cohort study with lung function assessments before the development of bronchiolitis together with the close clinical follow-up to the research clinic and daily symptom recordings assuring ascertainment of all severe episodes. Lung function measurements were completed in a large group of asymptomatic infants (404) within a narrow age-range around 1 month after birth. This is the largest study of lung function in neonates under standardized conditions. Baseline lung function was conducted by infant spirometry adapted as the state-of-the-art Raised Volume Rapid Thoracic Compression technique which provides flowvolume measures. The previous analyses found PtcO 2 was the most sensitive parameter for detection changes in lung function (dose-response curve metacholine challenge), followed by FEV 0.5 , both superior to other indexes of forced spirometry as well as all tidal breathing indexes (25, 27). We analyzed bronchial responsiveness as a quantitative trait in the RSV and control group rather than dichotomizing the infants into +/- hyperresponsiveness. All cases of non-RSV bronchiolitis and acute severe wheeze episodes were excluded from the control group, which would tend to favor a difference between our cases and controls. Nineteen of the 22 infants (86%) with RSV bronchiolitis were hospitalized. Danish children are generally only admitted if they need support with feeding tube, suction of upper airways, mask inhalations or nasal continuous positive airway pressure, which ensures a certain severity in their RSV infection in our study. Confounder adjustment included mothers smoking during 3 rd trimester and gender both well known risk factors for bronchiolitis (41-47). We found an overweight of boys (73%) in the RSV group in agreement with previous reports (41-43, 48, 49). Lung function measurement data were calibrated for birth length and lifespan at examination date because these parameters have shown to affect early lung function in the COPSAC cohort (29). 6
Meaning of the study Acute RSV bronchiolitis may occur in otherwise healthy infants. Infants with bronchiolitis are at significant risk for subsequent recurrent wheezing and childhood asthma (11, 50-53). It is not known whether viral bronchiolitis is causatively related to asthma or simply identifies infants at risk for subsequent wheezing from an atopic predisposition or pre-existing abnormal lung function (54, 55). Infants with impaired pulmonary function at one month of age was reported to be prone to recurrent wheezy episodes and asthma (8-11, 13, 14, 56, 57). Therefore it has been assumed that acute bronchiolitis or wheeze develop due to pre-morbid abnormal pulmonary lung function consistent with smaller airway size (11, 12, 15, 18, 19). But these are indirect evidence as clinical wheezing illness was used as end-point This is the first study to look specifically at neonatal lung function before RSV bronchiolitis. Our study showed no association between early lung function (FEV 0.5 and bronchial hyperresponsiveness) and subsequent RSV bronchiolitis. This could mean that small airways were not the distinguishing feature of later development of RSV bronchiolitis. We recognize that the confidence interval of the comparison of baseline lung function was wide with the risk of type 2 error. Broughton et al. (2006) studied prospectively premature infants and found those who had symptomatic RSV lower respiratory tract infection had worse lung function (higher resistance) prior to neonatal unit discharge compared to controls but no difference in the lung volumes (functional residual capacity) (17). It is difficult to compare this study with our result since we used a different lung function technique. Future studies may consider using other lung function tests such as for example whole-body plethysmography measuring airway resistance. Studies using forced expiratory maneuvers have shown to discriminate normal infants and wheezy infants or infants with cystic fibrosis (58-60). These studies were done on older children (age > 3 months) and therefore not comparable with our data. A cross-sectional study of 37 normal infants found that a family history of asthma had a negative effect on FEV 0.5 (61). Another study on 63 normal healthy infants found that airway responsiveness in infancy was increased in families with history of asthma or parental smoking (56). Since our cohort only includes infants with asthmatic mothers the absolute levels of lung function and bronchial responsiveness may not be representative of the general population. However, this does not affect the purpose of comparing lung function of infants who later develop RSV bronchiolitis and infants 7
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Lung function measurements in child
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Contents Acknowledgements .........
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Acknowledgements The thesis was wri
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Introduction Symptoms of chronic re
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pulmonary function test obtained by
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I. Accuracy of Wholebody Plethysmog
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Methods Designs Study I: Six center
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"Loops" on the screen showed the re
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We included age in the analysis of
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Normative data (study I) Mean sRaw
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Additional results sRaw measurement
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After correcting the factory settin
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Normative data In the second part o
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II. -III. Lung function measurement
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of a diagnosis of asthma: Frequent
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Figure 8: Familial predisposition t
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Total twins 12.349 twin pairs Born
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Methods Designs Study II: Hospital
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Children less than 7 years were tes
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Ethics The two studies were approve
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FEV 0.5 (ml) Table 4: Baseline char
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lung symptoms, 19% said it was the
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symptoms in response to verified RS
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epigenetic factors. Acute environme
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detection changes in lung function
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that small airways were not the dis
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onciolitis. There is an increasing
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further studies are needed to inves
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Summary The Ph.D. thesis is based o
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Danish summary (Dansk resumé) Denn
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References Reference List (1) Lum S
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(25) Aurora P, Gustafsson P, Bush A
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(50) Klug B, Bisgaard H. Repeatabil
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(76) Meissner HC. Economic impact o
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(101) Young S, Arnott J, O'Keeffe P
Page 72 and 73: (125) Bisgaard H, Hermansen MN, Lol
Page 74 and 75: (151) Walton RP, Johnston SL. Role
Page 76 and 77: disease in otherwise healthy infant
Page 78 and 79: changes in asthma control. Am J Res
Page 81: Paper I
Page 84 and 85: CHEST Original Research Accuracy of
Page 86 and 87: Figure 1. Center agreement study: l
Page 88 and 89: observer as well as a common observ
Page 90 and 91: sRaw (kPa*s) Figure 1 Online: Cente
Page 93 and 94: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Page 95 and 96: 54 55 56 57 INTRODUCTION Respirator
Page 97 and 98: 97 98 99 100 Lung function test Chi
Page 99 and 100: 141 142 143 144 Mean gestational ag
Page 101 and 102: 186 187 188 189 190 The discordant
Page 103 and 104: 232 233 234 235 236 237 viruses and
Page 105 and 106: 278 ACKNOWLEDGMENTS 279 280 281 282
Page 107 and 108: 335 336 (21) Bisgaard H, Nielsen KG
Page 109 and 110: 394 395 396 (42) Wu P, Dupont WD, G
Page 111 and 112: 455 456 457 (64) Bisgaard H, Herman
Page 113 and 114: 488 489 Table 1: Comparison of clin
Page 115: Paper III
Page 118 and 119: Abstract Background: Two-three perc
Page 120 and 121: RA 08 TSM 133; Respiratory Care Cen
Page 124 and 125: who do not develop RSV bronchioliti
Page 126 and 127: Acknowledgements We thank all the c
Page 128 and 129: (24) ATS/ERS statement: raised volu
Page 130 and 131: (53) Stein RT, Sherrill D, Morgan W
Page 132 and 133: Figure 1: Flow chart COPSAC cohort
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