Lung function measurements in children - copsac

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II. -III. Lung function measurements before and after RSV Bronchiolitis Background Respiratory syncytial virus infection in infancy Respiratory syncytial virus (RSV) is a single-stranded RNA virus, a member of the family Paramyxoviridae, subfamily Pneumovirinae. RSV can be divided into two major antigenic groups, known as A and B, and each has several subtypes (69, 70). The virus was isolated first time in 1957, Baltimore, USA, from children with lower respiratory illness (71). Epidemiology Respiratory syncytial virus is a common cause of lower respiratory tract disease and hospitalization in otherwise healthy infants (72-75), and therefore a major cause of healthcare utilization (76). Recent data from the United States suggest that hospitalization rates caused by RSV infections are increasing (77). Two-three percent of infants react to RSV infection with bronchiolitis (inflammation of the small airways in the lung) before age 1 (77-80). A study in East Denmark estimated that 34/1000 infants below 6 months were hospitalized with RSV infection during one winter season (81). During the RSV-season from November to May approximately 1500 Danish children are hospitalized with RSV infection. High-risk groups for developing severe RSV infection include premature infants, children less than 2 years of age with congenital heart or chronic lung diseases or reduced immune-function. Most hospitalized infants are born at term and otherwise healthy; among this group the risk factors associated to RSV hospitalization are age under 6 months, male gender, month of birth, low socioeconomic status, crowded living conditions, siblings, parental smoking, day care attendance and family history of asthma and atopy (69). Passive prophylaxis (Palivizumab) against RSV has been available since 1998 and has reduced RSV hospitalization 55% among high-risk infants (82-84). Palivizumab is expensive and only given prophylactic to high-risk infants. 26
Clinical manifestations RSV infection can be spread from an infected person up to three weeks after symptom debut by sending virus-containing droplets into the air when coughing or sneezing. The droplets remain contagious on environmental surfaces more than 6 hours and can infect a person when it comes in contact with mouth, nose or eye. Common symptoms of RSV infection are upper respiratory infection and coryza. Most recover from RSV infection within 1 to 2 weeks. However, in 25-40 % of the primarily infected infants a RSV infection manifests as a lower respiratory tract infection, bronchiolitis or pneumonia. Infants with bronchiolitis have tachypnea, wheezes, chest retractions and in the youngest infants risk of apnea (69, 85). Almost all children are infected with the virus by their second birthday, but only a small percentage develops severe disease. Asthma in childhood Asthma in young children is associated with high morbidity and the prevalence is increasing (86). Approximately 7% of Danish schoolchildren have asthma and 15-20 % of preschool children have episodes of asthmatic symptoms. This is the most common cause of hospitalization of young children in Denmark (87). Definition Asthma is a chronic inflammatory disorder of the airways. The mechanism involves several inflammatory cells (mast cells, eosinophils, Th2 etc.) which release mediators that contribute to airway narrowing: the airway smooth muscle contracts; increased microvascular leakage lead to airway oedema; mucus hypersecretion; and airway thickening (“remodelling”). Asthma has significant genetic and environmental components, but since its pathogenesis is not clear, much of its definition is descriptive (86). Clinical manifestations and diagnosis The chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. Following symptoms are highly suggestive 27
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 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 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
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CHEST Original Research Accuracy of
Page 86 and 87:
Figure 1. Center agreement study: l
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observer as well as a common observ
Page 90 and 91:
sRaw (kPa*s) Figure 1 Online: Cente
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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
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97 98 99 100 Lung function test Chi
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141 142 143 144 Mean gestational ag
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186 187 188 189 190 The discordant
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232 233 234 235 236 237 viruses and
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278 ACKNOWLEDGMENTS 279 280 281 282
Page 107 and 108:
335 336 (21) Bisgaard H, Nielsen KG
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394 395 396 (42) Wu P, Dupont WD, G
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455 456 457 (64) Bisgaard H, Herman
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488 489 Table 1: Comparison of clin
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Paper III
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Abstract Background: Two-three perc
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RA 08 TSM 133; Respiratory Care Cen
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prospectively if baseline lung func
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who do not develop RSV bronchioliti
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Acknowledgements We thank all the c
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(24) ATS/ERS statement: raised volu
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(53) Stein RT, Sherrill D, Morgan W
Page 132 and 133:
Figure 1: Flow chart COPSAC cohort
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