Lung function measurements in children - copsac

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lung symptoms, 19% said it was the control twin and 27% said both twins had comparable symptoms. 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. Furthermore, it would be impossible to make a subgroup analysis restricted to the twin pairs where the parents’ memories and data agreed. The study group would be very small. It is known that male sex could be a risk factor for RSV hospitalization (140-142). In the whole twin cohort the boys had a higher prevalence of severe RSV infection compared to the girls; odds ratio 1.20; CI [1.07-1.33] as previously presented by Thomsen et al. (2008) (115), but there was a random overrepresentation of females in our study (subgroup). 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) (115). The differences were small and not significant; therefore it seems that the discordant twins were representative of MZ twins in general. On the other hand it may bias the result because premature infants as a population have its own risk factors for impaired lung function. 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. The highest incidence of hospitalization for RSV-bronchiolitis is often reported in the 0- 1-yr-olds (113, 114, 143, 144). However, the reported mean age may be biased from excluding older children from such analyses. For example Sigurs et al. reported mean age of RSV hospitalization to be 3.5 months excluding infants older than 12 months (98, 98). Fjaerli et al. reported admission age median to be 6 months in children under two years old in their study (140). One study included children up to 2 years and 42
showed the median age of hospitalization was 10 months of age similar to our findings (145). 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. 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 (96) and most cases of asthma debut before school age. 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 function in childhood (94-99). One particular cohort study reported an asthma rate of 43% versus 8% and sensitization to common allergens of 45% versus 26% by age 13 years in children with infant hospitalization for RSV bronchiolitis compared with a matched control group (98). A review of pooled data from 10 controlled studies concluded that wheezing (but not recurrent wheezing) is more common after severe RSV bronchiolitis up till 5 years of follow-up (146). Two Finnish studies reported only marginally increase in the prevalence of asthma after RSV bronchiolitis in infancy (145, 147). On the other hand, predisposition to asthma and atopy was associated with increased risk of lower respiratory tract infection and hospitalization for RSV infection (112, 113, 116) and early wheezy symptoms were found to be a strong risk factor for subsequent hospitalisation for RSV (114). Therefore the direction of causality is unknown: Does RSV increase risk of asthma or is asthma constitution increasing the risk of severe response to RSV infection, or are both sharing a common undisclosed environmental exposure. The model we used adjusted for genetic variation by analyzing long-term outcome in monozygotic twin pairs, in which one infant had been hospitalized for severe lung 43
Page 1: Lung function measurements in child
Page 4 and 5: Contents Acknowledgements .........
Page 6 and 7: Acknowledgements The thesis was wri
Page 8 and 9: Introduction Symptoms of chronic re
Page 10 and 11: pulmonary function test obtained by
Page 12 and 13: I. Accuracy of Wholebody Plethysmog
Page 14 and 15: Methods Designs Study I: Six center
Page 16 and 17: "Loops" on the screen showed the re
Page 18 and 19: We included age in the analysis of
Page 20 and 21: Normative data (study I) Mean sRaw
Page 22 and 23: Additional results sRaw measurement
Page 24 and 25: After correcting the factory settin
Page 26 and 27: Normative data In the second part o
Page 28 and 29: II. -III. Lung function measurement
Page 30 and 31: of a diagnosis of asthma: Frequent
Page 32 and 33: Figure 8: Familial predisposition t
Page 34 and 35: Total twins 12.349 twin pairs Born
Page 36 and 37: Methods Designs Study II: Hospital
Page 38 and 39: Children less than 7 years were tes
Page 40 and 41: Ethics The two studies were approve
Page 42 and 43: FEV 0.5 (ml) Table 4: Baseline char
Page 46 and 47: symptoms in response to verified RS
Page 48 and 49: 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 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 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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