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It is unknown why respiratory syncytial virus (RSV) causes mild disease in some children and severe disease, requiring hospitalisation, in others. We aimed to assess whether diminished premorbid lung function in healthy term infants predisposes to hospitalisation during RSV bronchiolitis, and to post-RSV wheeze. In a prospective birth cohort study of unselected term healthy children, neonatal lung function was measured before the age of 2 months (n=2133). From birth through the first year of life, respiratory symptoms were recorded in a diary, and general practitioner consultations and hospitalisations were documented. In a subgroup (n=417) repeated nose and throat swabs were collected for PCR to detect RSV infections. Median neonatal respiratory system compliance (Crs) was significantly lower (41.2 versus 47.4 mL · kPa(-1), p=0.03) and resistance (Rrs) was higher (8.2 versus 6.3 kPa · s · L(-1), p=0.10) in hospitalised RSV patients (n=18) compared with nonhospitalised RSV-positive infants (n=84). Every 10 mL · kPa(-1) increase in Crs was associated with 55% less post-RSV wheeze (OR 0.56, 95% CI 0.35-0.90), and each kPa · s · L(-1) increase in Rrs was associated with 42% more post-RSV wheeze, which was only marginally explained by pre-RSV wheeze or severity of the RSV disease. This unselected birth cohort study shows for the first time that decreased lung function at birth predisposes to severe RSV disease, and to post-RSV wheeze., (©ERS 2014.)

Objectives: Human rhinoviruses (HRVs) have been suggested to play a role in the development of childhood wheezing. However, whether HRV is causally related to the development of wheezing or HRV-associated wheeze is merely an indicator of disease susceptibility is unclear. Our aim was to study the role of HRV during infancy in the development of lower respiratory disease during infancy and childhood., Methods: In a population-based birth cohort, during the 1st year of life, nose and throat swabs were collected on a monthly basis, regardless of any symptoms. Polymerase chain reaction was used to detect an extensive panel of respiratory pathogens. Lung function was measured before 2 months of age. Information on respiratory symptoms was collected by daily questionnaires and electronic patient files., Results: 1425 samples were collected in 140 infants. Both the presence of (single or multiple) pathogens (HRV equal to other pathogens) and increased respiratory system resistance were significantly associated with lower respiratory symptoms during infancy. HRV presence during infancy was not associated with the risk of wheezing at age 4, but every HRV episode with wheezing increased the risk of wheezing at age 4 (odds ratio 1.9, 1.1-3.5). This association weakened after adjustment for lung function (odds ratio 1.4, 0.7-2.9)., Conclusions: HRV and other viruses are associated with lower respiratory symptoms during infancy, as well as a high presymptomatic respiratory system resistance. HRV presence during infancy is not associated with childhood wheezing, but wheeze during a HRV episode is an indicator of children at high risk for childhood wheeze, partly because of a reduced neonatal lung function.

Studies of reduced neonatal lung function and wheezing illnesses during childhood show conflicting results. The aim of our study was to assess the association between resistance (Rrs) and compliance (Crs) of the respiratory system by using the single occlusion technique (SOT) and prospectively collected wheezing illnesses during the first 5 years of life in a large birth cohort. SOT was performed during natural sleep before the age of 2 months. Information about wheezing illnesses was collected from the electronic patient file. 549 infants had a successful SOT measurement and complete medical records. Every kPa·L(-1)·s(-1) increase in Rrs was associated with 10% more consultations in the first 3 years of life. Every 10 mL·kPa(-1) increase in Crs was associated with a 14% reduction in consultations in the first 3 years of life, 27% in the fourth to fifth years of life, and a lower probability of having asthma at the age of 5 years (OR 0.66). Children with late-onset or persistent wheezing had significant lower Crs values than their peers. An increased neonatal resistance is associated with more wheezing illnesses during infancy, while a reduced neonatal compliance is associated with more wheezing illnesses during the first 5 years of life, a late-onset or persistent wheezing phenotype, and asthma.

Abnormal early life lung function is related to wheezing in childhood; however, data on the association with cough are not available. We determined the relationship between early life lung function and wheeze and cough during the first year of life, adjusted for other possible risk factors. Infants were participants of the Wheezing Illnesses Study Leidsche Rijn (WHISTLER). Lung function measurements were performed before the age of 2 months. Information on pre- and perinatal factors, general characteristics and anthropometrics were assessed by questionnaires. Follow-up data on respiratory symptoms were assessed by daily questionnaires. 836 infants had valid lung function measurements and complete follow-up data for respiratory symptoms at 1 yr of age. Multivariable Poisson analysis showed that higher values of respiratory resistance (R(rs)) and time constant (τ(rs)) were associated with an increased risk for wheeze and cough during the first year of life. Higher values of respiratory compliance (C(rs)) were associated with a decreased risk for wheeze and cough. R(rs), C(rs) and τ(rs) measured shortly after birth were independently associated with wheeze and cough during the first year of life. As the strength of the relationships were different for wheeze and cough, they should be used as two separate entities.

The aim of our study was to investigate the association between rapid weight gain in the first 3 months of life and the prevalence of wheeze in the first years of life and lung function at 5 yrs of age. The infants selected were participating in an ongoing birth cohort. Information on growth and respiratory symptoms was collected during the first year of life, and on primary care consultations during total follow-up. Forced expiratory volume in 1 s (FEV(1)) and forced expiratory flow at 25-75% of forced vital capacity (FEF(25-75%)) were measured at 5 yrs of age. Information on growth and respiratory symptoms was obtained for 1,431 infants, out of whom 235 children had already had 5 yrs of follow-up. Every one-point z-score increase in weight gain resulted in a 37% increase in days with wheeze (incidence rate ratio 1.37, 95% CI 1.27-1.47; p<0.001) and in associated consultations by 16% (incidence rate ratio 1.16, 95% CI 1.01-1.34; p=0.04). Children with rapid weight gain reported significantly more physician-diagnosed asthma. FEV(1) and FEF(25-75%) were reduced by 34 mL (adjusted regression coefficient -0.034, 95% CI -0.056- -0.013; p=0.002) and 82 mL (adjusted regression coefficient -0.082, 95% CI -0.140- -0.024; p=0.006) per every one-point z-score increase in weight gain, respectively. These associations were independent of birthweight. Rapid early weight gain is a risk factor for clinically relevant wheezing illnesses in the first years of life and lower lung function in childhood.