Lung function measurements in children - copsac
Lung function measurements in children - copsac Lung function measurements in children - copsac
FEV 0.5 (ml) Table 4: Baseline characteristics Total COPSAC Control group RSV bronchiolitis Baseline lung function (FEV 0.5 /ml) 404 Number Mean (SD) Median 360 66.3 (12.9) 65.8 21 65.5 (13.0) 63.6 PD 15 363 Number 322 20 (PTcO 2 /mmol) Mean (SD) 1.81 (12.2) 0.59 (0.88) Median 0.33 0.16 Baseline FEV 0.5 did not differ between infants with RSV bronchiolitis compared with the control group: OR 1.08 [0.09-13.6], p=0.95 (figure 11); z-score -0.06. Bronchial responsiveness did not differ between infants with RSV bronchiolitis compared with the control group: OR 0.94 [0.74-1.20], p-value 0.64. 120 100 80 60 40 RSV control 20 0 40,0 50,0 60,0 70,0 Length (cm) Figure 11: Neonatal baseline lung function versus body length 40
Discussion Twin study We found no difference within co-habiting MZ twin pairs discordant for hospitalization for RSV bronchiolitis in infancy on the asthma prevalence, baseline lung function, bronchial responsiveness; biomarker of airway inflammation (F E NO) and sensitization 7 years after such severe RSV bronchiolitis. Limitations and Strengths of the study design Monozygotic twins were useful for investigating the role of genetic and environmental factors on asthma because of their identical genetic background and similar childhood environmental exposures. However, comparison of MZ twin pairs discordant to hospitalization for RSV bronchiolitis was prone to a number of biases. We had no evidence to prove that the twin serving as control was actually infected with RSV, but rely on very high virulence of RSV among cohabitating twins previously estimated to 93-96% (115) though this could not be verified. In an optimal study there would have been comparable nasopharyngeal aspirates from the twin pair to quantify RSV virus load (136-138) or a blood sample measuring RSV serum antibodies to detect any difference in association to disease severity (139). Thomsen et al. (2008) reported that in the whole twin cohort the proband-wise concordance rate of hospitalization for RSV-bronchiolitis was significantly higher in MZ (0.66) than in DZ twin pairs (0.53), p=0.02 (115). The decision to hospitalize may have been influenced by local policies such as number of available rooms and the assessment of disease severity varied by different physicians, but this would not influence the fact that only one twin was hospitalized and the other was not. We do not have positive evidence that the control twin had milder symptoms, but rely on the fact that one was hospitalized while the other was not. Danish children are generally only admitted with RSV infection 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, fifty-four% of the parents answered retrospectively that the hospitalized RSV proband twin suffered more severe 41
- 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 44 and 45: lung symptoms, 19% said it was the
- 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
Discussion<br />
Tw<strong>in</strong> study<br />
We found no difference with<strong>in</strong> co-habit<strong>in</strong>g MZ tw<strong>in</strong> pairs discordant for hospitalization<br />
for RSV bronchiolitis <strong>in</strong> <strong>in</strong>fancy on the asthma prevalence, basel<strong>in</strong>e lung <strong>function</strong>,<br />
bronchial responsiveness; biomarker of airway <strong>in</strong>flammation (F E NO) and sensitization 7<br />
years after such severe RSV bronchiolitis.<br />
Limitations and Strengths of the study design<br />
Monozygotic tw<strong>in</strong>s were useful for <strong>in</strong>vestigat<strong>in</strong>g the role of genetic and environmental<br />
factors on asthma because of their identical genetic background and similar childhood<br />
environmental exposures. However, comparison of MZ tw<strong>in</strong> pairs discordant to<br />
hospitalization for RSV bronchiolitis was prone to a number of biases.<br />
We had no evidence to prove that the tw<strong>in</strong> serv<strong>in</strong>g as control was actually <strong>in</strong>fected with<br />
RSV, but rely on very high virulence of RSV among cohabitat<strong>in</strong>g tw<strong>in</strong>s previously<br />
estimated to 93-96% (115) though this could not be verified. In an optimal study there<br />
would have been comparable nasopharyngeal aspirates from the tw<strong>in</strong> pair to quantify<br />
RSV virus load (136-138) or a blood sample measur<strong>in</strong>g RSV serum antibodies to detect<br />
any difference <strong>in</strong> association to disease severity (139). Thomsen et al. (2008) reported<br />
that <strong>in</strong> the whole tw<strong>in</strong> cohort the proband-wise concordance rate of hospitalization for<br />
RSV-bronchiolitis was significantly higher <strong>in</strong> MZ (0.66) than <strong>in</strong> DZ tw<strong>in</strong> pairs (0.53),<br />
p=0.02 (115).<br />
The decision to hospitalize may have been <strong>in</strong>fluenced by local policies such as number<br />
of available rooms and the assessment of disease severity varied by different physicians,<br />
but this would not <strong>in</strong>fluence the fact that only one tw<strong>in</strong> was hospitalized and the other<br />
was not.<br />
We do not have positive evidence that the control tw<strong>in</strong> had milder symptoms, but rely<br />
on the fact that one was hospitalized while the other was not. Danish <strong>children</strong> are<br />
generally only admitted with RSV <strong>in</strong>fection if they need support with feed<strong>in</strong>g tube,<br />
suction of upper airways, mask <strong>in</strong>halations or nasal cont<strong>in</strong>uous positive airway pressure.<br />
Yet, this could be biased from registration practice. Indeed, fifty-four% of the parents<br />
answered retrospectively that the hospitalized RSV proband tw<strong>in</strong> suffered more severe<br />
41