Our findings are consistent with infants with BPD having impaired alveolar development with fewer but larger alveoli, as well as a reduced Vc.

Childhood asthma is often characterised by elevated exhaled nitric oxide (eNO), decreased lung function, increased airway reactivity and atopy; however, our understanding of when these phenotypic airway characteristics develop remains unclear. This study evaluated whether eNO, lung function, airway reactivity and immune characteristics during infancy are risk factors of asthma at age 5 years. Infants with eczema, enrolled prior to wheezy illness (n=116), had eNO, spirometry, airway reactivity and allergen sensitisation assessed at entry to the study and repeated at age 5 years (n=90). Increasing eNO at entry was associated with an increased risk of asthma (p=0.037) and increasing airway reactivity (p=0.015) at age 5 years. Children with asthma at 5 years of age had a greater increase in eNO between infancy and age 5 years compared with those without asthma (p=0.002). Egg sensitisation at entry was also associated with an increased risk of asthma (p=0.020), increasing eNO (p=0.002) and lower forced expiratory flows (p=0.029) as a 5 year-old. Our findings suggest that, among infants at high risk for developing asthma, eNO early in life may provide important insights into the subsequent risk of asthma and its airway characteristics.

Angiogenesis is a critical determinant of alveolarisation, which increases alveolar surface area and pulmonary capillary blood volume in infants; however, our understanding of this process is very limited. The purpose of our study was to measure the pulmonary membrane diffusion capacity (DM) and pulmonary capillary blood volume (VC) components of the diffusing capacity of the lung for carbon monoxide (DLCO) in healthy infants and toddlers, and evaluate whether these components were associated with pro-angiogenic circulating haematopoietic stem/progenitor cells (pCHSPCs) early in life.21 healthy subjects (11 males), 3-25 months of age, were evaluated. DLCO was measured under normoxic and hyperoxic conditions, and DM and VC were calculated. From 1 mL venous blood, pCHSPCs were quantified by multiparametric flow cytometry.DM and VC increased with increasing body length; however, membrane resistance as a fraction of total resistance to pulmonary diffusion remained constant with somatic size. In addition, DLCO and VC, but not DM, increased with an increasing percentage of pCHSPCs.The parallel increase in the membrane and vascular components of pulmonary diffusion is consistent with alveolarisation during this period of rapid lung growth. In addition, the relationship between pCHSPCs and VC suggest that pro-angiogenic cells may contribute to this vascular process. @ERSpublications Vascular components of pulmonary diffusion are associated with circulating pro-angiogenic cells in infants and toddlers

Pulmonary interstitial glycogenosis (PIG) is an idiopathic interstitial lung disease of infants. The underlying pulmonary pathophysiology of PIG has not been well characterized. Herein we report a term-gestation infant who presented with persistent tachypnea and hypoxia. A chest CT scan demonstrated a diffuse ground glass appearance and lung biopsy demonstrated increased alveolar septae cellularity with glycogen-containing cells, consistent with a diagnosis of PIG. At 3 months of age, pulmonary function testing included: pre- and post-bronchodilator forced expiratory flows using the raised-volume technique and the ratio of pulmonary diffusing capacity for carbon monoxide to alveolar volume (DLCO /VA ). He was prescribed 5 days of oral prednisolone (2mg/kg/day) and pulmonary function testing (PFT) was repeated at 5, 13, and 20 months of age. Initial PFTs demonstrated reduced forced vital capacity (FVC: Z-score = -2.36) and an increased ratio of forced expiratory volume in 0.5 sec to FVC (FEV0.5/FVC: Z-score = 1.15) with no significant change following an inhaled bronchodilator. There was also a marked reduction in DLCO /VA (Z-score = -4.74) compared to age-matched controls. Follow-up demonstrated progressive clinical improvement as well as an increase in Z-FVC and normalization of DLCO /VA . Our in vivo physiological findings are consistent with previous reports that symptom resolution correlated with histological thinning of the alveolar septae upon repeat lung biopsy. The restrictive lung disease we observed is consistent with expected reduced compliance of an alveolar interstitial lung process like PIG, whereas the absence of a reduction in FEV0.5/FVC confirms the absence of obstructive airway disease.

Summary Rationale While infants who are born extremely premature and develop bronchopulmonary dysplasia (BPD) have impaired alveolar development and decreased pulmonary diffusion (DLCO), it remains unclear whether infants born less premature and do not develop BPD, healthy premature (HP), have impaired parenchymal development. In addition, there is increasing evidence that pro-angiogenic cells are important for vascular development; however, there is little information on the relationship of pro-angiogenic cells to lung growth and development in infants. Objective and Methods Determine among healthy premature (HP) and fullterm (FT) infants, whether DLCO and alveolar volume (VA) are related to gestational age at birth (GA), respiratory support during the neonatal period (mechanical ventilation [MV], supplemental oxygen [O2], continuous positive airway pressure [CPAP]), and pro-angiogenic circulating hematopoietic stem/progenitor cells (CHSPCs). We measured DLCO, VA, and CHSPCs in infants between 3–33 months corrected-ages; HP (mean GA = 31.7wks; N = 48,) and FT (mean GA = 39.3wks; N = 88). Result DLCO was significantly higher in HP than FT subjects, while there was no difference in VA, after adjusting for body length, gender, and race. DLCO and VA were not associated with GA, MVandO2; however, higher values were associated with higher CHSPCs, as well as treatment with CPAP Conclusion Our findings suggest that in the absence of extreme premature birth, as well as BPD, prematurity per se, does not impair lung parenchymal development.

Background: Exhaled nitric oxide (eNO) has been proposed for monitoring airway inflammation, diagnosis, and prediction of steroid responsiveness in asthma. However, its utility after elective suspension of asthma medication is still unclear. We aimed to determine the association between eNO values and the subsequent loss of asthma control (LAC) in asymptomatic asthmatic children after inhaled corticosteroids (ICS) withdrawal. Methods:We conducted a prospective observational cohort study. Forty-two children (23 boys), mean age 11 years, with clinically controlled asthma, according to GINA guidelines, and receiving low-dose of ICS (budesonide 200 μg/day or equivalent) were included immediately after the withdrawal of ICS. eNO, Asthma Control Test (ACT) and spirometry were monthly assessed, during 54 weeks or until the presence of at least one of the following criteria of LAC: 1) asthma exacerbation, 2) obstructive spirometric pattern, 3) ACT ≤ 19.Results: eNO baseline geometric mean (eNO b ), measured 4 weeks after discontinuation of ICS, was 23.7 ppb (SD: 1.16). An eNO b cutoff point of 21.8 ppb was determined to better discriminate between high and low eNO groups. Twenty-five subjects (71.4%) had LAC. High eNO b was associated to LAC (OR: 9.01; 95CI: 1.10-74.26). In addition, LAC occurred earlier in high eNO b than in low eNO b patients (8 vs 28 weeks, respectively; P = 0.017). Conclusions:Our findings suggest that eNO predicts loss of asthma control and may contribute for clinical follow up decisions during childhood asthma after ICS withdrawal. K E Y W O R D Sasthma, exhaled nitric oxide, inhaled corticosteroids

Childhood asthma is characterized by atopy, airway hyper-reactivity, and airway inflammation; however, it remains unclear how Rationale these relationships develop from very early in life. We previously described that infants mean age 11 months with eczema (atopic or non-atopic) have lower forced expiratory flows, heightened airway reactivity, and elevated exhaled nitric oxide (eNO) prior to any episodes of wheezing (JACI 2008 Oct;122(4):760-5).: At 5-years of age, we have so far obtained longitudinal follow-up measurements in 65 of the 116 subjects. At entry to the study, Methods blood was obtained to assess specific IgE to a panel of 10 allergens, and peripheral blood mononuclear cells (PBMC) were isolated and stimulated to assess cytokine production. Spirometry, airway reactivity to inhaled methacholine, and exhaled nitric oxide (eNO) were measured during infancy and at 5-year follow-up. We evaluated the relationship between these measurements and Current asthma at 5-years of age, which was defined by 1) any episode of wheezing during the past year and asthma diagnosis by a physician, or 2) use of asthma medication within the past year.: Subjects with Current Asthma (N = 43) compared to those without Current Asthma (N = 22) had more frequent sensitization to Results egg and/or milk (37.84% vs 5.26%, p = 0.009), lower spirometry (ZFEF25-25, -0.66 vs 0.16, p = 0.014), a greater percent decrease in FEV1 with methacholine challenge (33.0% vs. 20.11%, p = 0.012), and higher eNO (p = 0.012). At entry to the study, prior to wheezing, predictors of Current Asthma at 5-years of age included: eNO (OR: 4.867, p = 0.048), any positive allergen-specific IgE (OR: 3.520, p = 0.036), and greater IL-5 production from stimulated PBMCs (OR: 6.725, p = 0.028). In addition, sensitization to egg and/or milk (p = 0.034) and higher SCORAD (p = 0.010) upon entry to the study were associated with lower spirometry (FEF25-75) in 5-year olds. Lastly, lower spirometry (FEF25-75; p = 0.015) and higher eNO (p = 0.016) upon entry to the study were associated with greater airway reactivity at 5-years of age.: Our findings suggest that atopy, increased cytokine production, airway inflammation, and low lung function early in life, prior Conclusion to the onset of wheezing, may be early biomarkers in the natural history of childhood asthma. This abstract is funded by: NIH grants #HL080071, AI070448 and AI057459 Am J Respir Crit Care Med 185;2012:A2339 Internet address: www.atsjournals.org Online Abstracts Issue

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