Lung function measurements in children - copsac

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epigenetic factors. Acute environmental factors are directly associated with epigeneticdependent disease phenotypes (165-167). Speculations may consider differing coinfections with an agent of less virulence including bacterial colonization (126, 168) or other viral infections. There is increasing evidence that rhinoviruses (RV) are able to cause lower airway infections and to induce wheezing in young children, and it may be as common as RSV as a cause of bronchiolitis (142, 169-171). Human metapneumovirus (hMPV) has also recently been recognised as one of several other viral pathogens that can cause acute bronchiolitis in infants (172, 173), the remaining being mainly parainfluenzavirus and adenovirus. However, the long-term effect of this and other viral agents on lung function and symptoms later in childhood is not yet fully investigated. Neonatal lung function Principal findings We found no association between baseline lung function and bronchial responsiveness in neonates and later development of bronchiolitis with RSV infection compared to the control group. Limitations and Strengths We used strict definition of bronchiolitis in accordance with a recent review (127). Our definition of bronchiolitis is consistent with the Anglo-Saxon definition including widespread fine crepitations and sometimes expiratory rhonchi on auscultation in the definition (127, 174-176). In the American literature, the definition sometimes includes all first-time wheezing infants with associated respiratory-tract infection (144, 177, 178). We recognize the lack of evidence for the effect of steroids for bronchiolitis (179- 184) but took the pragmatic approach to include their use in our definition of the more acute cases realizing this is a well established clinical practice and indicating a certain clinical severity. Also, we recognize that the diagnosis of acute bronchiolitis is likely to comprise infants with first acute attack of asthma, but this would have biased the risk estimates against the null hypothesis assuming such infants with underlying asthma would have had reduced lung function and bronchial hyperresponsiveness. 46
The confidence interval of the comparison of baseline lung function includes a wide interval from 0.09 to 13.6 (risk of type 2 error), suggesting the need for an unlikely study size to ever decide 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 flow-volume measures overall in agreement with ATS/ERS standards (2). The method of the study differs from the ATS/ERS guidelines in few points, for example it is recommended to deliver an inflation pressure of 30 H 2 O cm ~ 2.9 kPa. A previous publication by Loland and Bisgaard commented the safety in the study (123) and recognized that FEV 0.5 measured in this study may reflect forced flows at lower lung volumes than FEV 0.5 measured from a 3-kPa inflation pressure. On the other hand the lower compression pressures and obtaining flows at lower lung volumes could give advantages in the success rate for the detection of physiologic change and safety in terms of lower risk for aspiration. The commonly reported parameters calculated from RVRTC are as follows: FVC, FEV 0.5 , FEF 50 , FEF 75 , FEF 85 and FEF 25-75 and in infants younger than 3 months also FEV 0.4 . However, it is not recommended to report maximal flow at FRC (V´max FRC ) from RVRTC because it is likely to be highly variable; tidal flow parameters are hardly mentioned in the ATS/ERS recommendations (2). Most of the recommended parameters were measured (FVC, FEF 25 , FEF 50 , FEF 75 and tidal flow parameters) but not reported in this thesis. The previous analyses found PtcO 2 was the most sensitive parameter for 47
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 44 and 45: lung symptoms, 19% said it was the
Page 46 and 47: symptoms in response to verified RS
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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