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BACKGROUND A positive effect of breastfeeding on lung function has been demonstrated in cohorts of children with asthma or risk for asthma. We assessed the impact of breastfeeding on lung function and symptoms at the age of 6 years in an unselected, healthy birth cohort. METHODS We prospectively studied healthy term infants from the Bern-Basel Infant Lung Development (BILD) cohort from birth up to 6 years. Any breastfeeding was assessed by weekly phone calls during the first year of life. Risk factors (eg, smoking exposure, parental history of allergic conditions, and education) were obtained using standardized questionnaires. The primary outcomes were lung function parameters measured at 6 years of age by spirometry forced expiratory volume in 1 second, body plethysmography (functional residual capacity [FRCpleth ], the total lung capacity [TLCpleth ], and the effective respiratory airway resistance [Reff ]) and fractional exhaled nitric oxide (FeNO). Secondary outcomes included ever wheeze (between birth and 6 years), wheeze in the past 12 months, asthma, presence of allergic conditions, atopic dermatitis, rhinitis, and positive skin prick test at the age of 6 years. RESULTS In 377 children the mean breastfeeding duration was 36 weeks (SD 14.4). We found no association of breastfeeding duration with obstructive or restrictive lung function and FeNO. After adjustment for confounders, we found no associations of breastfeeding duration with respiratory symptoms or the presence of allergic conditions. CONCLUSION This study found no evidence of an association between breastfeeding and comprehensive lung function in unselected healthy children with long-term breastfeeding. Our findings do not support the hypothesis that the duration of breastfeeding has a direct impact on lung function in a healthy population with low asthmatic risk.

Background: Adverse effects of higher air pollution levels before and after birth on subsequent lung function are often reported in the literature. We assessed whether low-to-moderate levels of air pollution during preschool-age impact upon lung function at school-age. Methods: In a prospective birth cohort of 304 healthy term-born infants, 232 (79%) completed lung function at follow-up at six years. Using spatial-temporal models, levels of individual air pollution (nitrogen dioxide (NO2) and ozone (O3), particulate matter with a diameter

The term "precision medicine" has become very popular over recent years, fuelled by scientific as well as political perspectives. Despite its popularity, its exact meaning, and how it is different from other popular terms such as "stratified medicine", "targeted therapy" or "deep phenotyping" remains unclear. Commonly applied definitions focus on the stratification of patients, sometimes referred to as a novel taxonomy, and this is derived using large-scale data including clinical, lifestyle, genetic and further biomarker information, thus going beyond the classical "signs-and-symptoms" approach.While these aspects are relevant, this description leaves open a number of questions. For example, when does precision medicine begin? In which way does the stratification of patients translate into better healthcare? And can precision medicine be viewed as the end-point of a novel stratification of patients, as implied, or is it rather a greater whole?To clarify this, the aim of this paper is to provide a more comprehensive definition that focuses on precision medicine as a process. It will be shown that this proposed framework incorporates the derivation of novel taxonomies and their role in healthcare as part of the cycle, but also covers related terms.

BACKGROUND Phenotypes of childhood-onset asthma are characterized by distinct trajectories and functional features. For atopy, definition of phenotypes during childhood is less clear. OBJECTIVE We sought to define phenotypes of atopic sensitization over the first 6 years of life using a latent class analysis (LCA) integrating 3 dimensions of atopy: allergen specificity, time course, and levels of specific IgE (sIgE). METHODS Phenotypes were defined by means of LCA in 680 children of the Multizentrische Allergiestudie (MAS) and 766 children of the Protection against allergy: Study in Rural Environments (PASTURE) birth cohorts and compared with classical nondisjunctive definitions of seasonal, perennial, and food sensitization with respect to atopic diseases and lung function. Cytokine levels were measured in the PASTURE cohort. RESULTS The LCA classified predominantly by type and multiplicity of sensitization (food vs inhalant), allergen combinations, and sIgE levels. Latent classes were related to atopic disease manifestations with higher sensitivity and specificity than the classical definitions. LCA detected consistently in both cohorts a distinct group of children with severe atopy characterized by high seasonal sIgE levels and a strong propensity for asthma; hay fever; eczema; and impaired lung function, also in children without an established asthma diagnosis. Severe atopy was associated with an increased IL-5/IFN-γ ratio. A path analysis among sensitized children revealed that among all features of severe atopy, only excessive sIgE production early in life affected asthma risk. CONCLUSIONS LCA revealed a set of benign, symptomatic, and severe atopy phenotypes. The severe phenotype emerged as a latent condition with signs of a dysbalanced immune response. It determined high asthma risk through excessive sIgE production and directly affected impaired lung function.

Rhinovirus (RV) infections occur early and recurrently in life, imposing a significant burden of disease on infants and young children. They are the most frequent causative agents of both upper and lower respiratory tract infections in this age group and are associated with a broad variety of clinical outcomes, ranging from asymptomatic infections to severe respiratory disease requiring hospitalisation. In addition to their impact on short-term morbidity, RVs are also debated as important pathogens in the development of recurrent wheeze and/or asthma. Several studies in infants at high-risk for atopy and asthma and in hospitalised children have demonstrated that recurrent wheezing illnesses induced by RVs early in life are a risk factor for the development of asthma later in childhood. However, underlying mechanisms are poorly understood. The question whether RVs are directly involved in the development of childhood wheeze and asthma, or whether symptomatic RV infections only represent a proxy for infants prone to develop obstructive lung diseases, is still open. In this review we provide an overview on the role of RVs as important disease-causing agents from infancy to early childhood and discuss their contribution to the subsequent development of childhood wheeze and/or asthma.

Background Although lung clearance index (LCI) is a sensitive indicator of mild cystic fibrosis (CF) lung disease it is rarely measured due to lengthy protocols and the commercial unavailability of multiple breath washout (MBW) setups and tracer gases. We used a newly validated commercially available nitrogen (N2) MBW setup to assess success rate duration and variability of LCI within a 20 min timeframe during clinical routine. We also evaluated the relationship between LCI and other clinical markers of CF lung disease. Methods One hundred thirty six children (83 with CF) between 4 and 16 years were studied in a pediatric CF outpatient setting. One hundred eighteen out of 136 children were naïve to MBW. Within 20 min each child was trained N2MBW was performed and LCI was analyzed. We assessed intra and between test reproducibility in a subgroup of children. Results At least one LCI was feasible in 123 (90) children with a mean (range) of 3.3 (1.2 6.4) min per test. Two or more measurements were feasible in 56 (41) children. Comparing LCI in CF versus controls LCI mean (SD) was 12.0 (3.9) versus 6.1 (0.9) and the intra and inter test coefficient of repeatability was 1.00 versus 0.81 and 0.96 versus 0.62 respectively. LCI was correlated with spirometry blood gases and Pseudomonas aeruginosa infection. Conclusions Using available N2MBW equipment LCI measurements are practical and fast in children. LCI is correlated with markers of CF lung disease. Longer timeframes would be required for triplicate N2MBW tests in inexperienced children. © 2012 Wiley Periodicals Inc.

Childhood asthma resembles a complex syndrome rather than a single disease. Clinical manifestations include cough, shortness of breath and wheeze. Because of its high prevalence, it is of major public health relevance. Presentation and disease course of childhood wheezing disorders vary, and its phenotypes are difficult to distinguish in early childhood despite the demand for diverse therapeutic strategies. Current treatments have no sustained effect on development of lung function and cannot prevent tracking of reduced lung function. Risk factors for childhood wheeze and subsequent asthma include genes, environmental factors and their interaction: all these affect lung development directly or indirectly (Figure 1). Data on the association between lung development and respiratory symptoms in early childhood are mostly derived from small hospital-based studies. Larger epidemiological studies have been based on questionnaires and most studies have been conducted in older children, in high-risk populations or retrospectively. There is a lack of prospectively assessed lung function studies in unselected healthy infants that take into account genetic and environmental factors. However, in order to disentangle the complex interaction of these predisposing factors on lung development and childhood wheeze, relatively large groups of infants need to be studied, with repeated lung function measurements, assessment of environmental and hereditary factors and clinical outcomes. The ‘Bern Infant Lung Development’ (BILD) cohort aims to contribute towards closing this gap. It was set up in 1999 to study physiological properties of the respiratory system and environmental and genetic risk factors affecting lung development in healthy individuals from infancy through childhood in relation to wheeze. How is it funded?