Lung function measurements in children - copsac

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164 165 166 167 The underlying assumption was that RSV sequelae were proportional to the severity of the RSV infection. We have no evidence to prove the twin serving as control was actually infected with RSV, but rely on very high virulence of RSV among cohabitating twins previously estimated at 93-96% (28) though this could not be verified. 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 We do not have positive evidence that this twin had milder symptoms, but rely on the fact that one was hospitalized while the other was not. 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. Yet, this could be biased from registration practice. Indeed, 19% of parents recalled the control twin being most severely affected. However, there is a significant risk for recall bias and the MZ pairs could be mixed up since the hospitalization was on average 7 years ago and parents were generally most unsure of the details. We could have restricted the analysis to the 20 pairs who recalled the proband twin to have been the most severely affected, but this was limited by the low numbers in the resulting analysis. Instead we relied on the Danish registration practice and included all 37 pairs. The distinction between possible "wheezers" and “bronchiolitis” may be inaccurate in this as in other studies. The distinction between wheezers and bronchiolitis is normally related to severity of wheeze and concurrent clinical signs of lower airway infection. Our samples included the latter, i.e. first hospitalization for severe wheeze with concomitant signs of lower airway infection. 183 184 185 It is known that male sex could be a risk factor for RSV hospitalization (30, 31). In the whole twin cohort there were more males than females in all outcomes (28), but there was a random overrepresentation of females in our study. 8
186 187 188 189 190 The discordant MZ twins in our study were born slightly earlier (mean gestational age 35.5 weeks and mean birth weight 2369 grams) than the MZ twins in the overall twin cohort (mean gestational age 36.1 weeks (SD 2.5) and birth weight 2498 grams (SD 549) (28). The differences were small and not significant; therefore it seems that the discordant twins were representative of MZ twins in general. 191 192 193 194 195 196 197 The highest incidence of hospitalization for RSV-bronchiolitis is often reported in the 0-1-yrolds (32-35). However, the reported mean age may be biased from excluding older children from such analyses. Fx Sigurs et al. reported mean age of RSV hospitalization to be 3.5 months excluding infants older than 12 months (10). Fjaerli et al. reported admission age median to be 6 months in children under two years old in their study (31). One study included children up to 2 years and showed the median age of hospitalization was 10 months of age similar to our findings (36). 198 199 200 201 Most importantly, the power of our study is limited by the low number of 37 paired cases, and the 95% confidential interval is correspondingly wide particularly for the clinical end-point though less so for the objective surrogate markers of asthma such as lung function and F E NO. However, our study was based on the complete national database and not power calculations. 202 203 204 205 Mean age at the clinical examination was 7.6 years. A difference in asthma prevalence later in life cannot be excluded but seems low inasmuch as those studies showing higher asthma prevalence after severe RSV found this mainly in early childhood (8) and most cases of asthma debut before school age. 206 207 208 Interpretation of the study We studied the direction of the causal relation between severe RSV bronchiolitis and asthma. RSV bronchiolitis has been associated with wheezing, asthma and abnormal pulmonary 9
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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
Page 50 and 51: detection changes in lung function
Page 52 and 53: that small airways were not the dis
Page 54 and 55: onciolitis. There is an increasing
Page 56 and 57: further studies are needed to inves
Page 58 and 59: Summary The Ph.D. thesis is based o
Page 60 and 61: Danish summary (Dansk resumé) Denn
Page 62 and 63: References Reference List (1) Lum S
Page 64 and 65: (25) Aurora P, Gustafsson P, Bush A
Page 66 and 67: (50) Klug B, Bisgaard H. Repeatabil
Page 68 and 69: (76) Meissner HC. Economic impact o
Page 70 and 71: (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: 141 142 143 144 Mean gestational ag
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 122 and 123: prospectively if baseline lung func
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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