Animal models suggest that reduced nitric oxide (NO) synthase activity results in lower values of exhaled NO (eNO) present at birth in those individuals who are going to develop chronic lung disease of infancy (CLDI).Online tidal eNO was measured in 39 unsedated pre-term infants with CLDI (mean gestational age (GA) 27.3 weeks) in comparison with 23 healthy pre-term (31.6 weeks) and 127 term infants (39.9 weeks) at 44 weeks post-conceptional age, thus after the main inflammatory response. NO output (NO output (V9NO)5eNO6flow) was calculated to account for tidal-flow-related changes. Sex, maternal atopic disease and environmental factors (smoking, caffeine) were controlled for.The mean eNO was not different (14.9 ppb in all groups) but V9NO was lower in CLDI compared with healthy term infants (0.52 versus 0.63 nL?s ). Values for healthy pre-term infants were between these two groups (0.58 nL?s -1 ). Within all pre-term infants (n562), V9NO was reduced in infants with low GA, high clinical risk index for babies scores and longer duration of oxygen therapy but not associated with post-natal factors, such as ventilation or corticosteroid treatment. After accounting for flow, the lower nitric oxide output in premature infants with chronic lung disease of infancy is consistent with the hypothesis of nitric oxide metabolism being involved in chronic lung disease of infancy.KEYWORDS: Chronic lung disease, infants, lung function, nitric oxide, prematurity R ecent evidence supports the hypothesis that chronic lung disease of infancy (CLDI) is the result of arrested or disturbed alveolar and vascular development [1]. The insult leading to this disturbed lung development may occur due to intra-uterine and postnatal infections, prematurity with surfactant deficiency or as a consequence of ventilation, hyperoxia (oxidative stress) or other factors. An inflammatory response with a peak at the age of ,10 days followed by a progressive decline [2] has been observed in this condition; however, little is known about the ongoing effects of these mechanisms after the acute phase during the first month of life.Various inflammatory processes, with a dominance of neutrophilic inflammation and oxidative stress, are involved in the pathogenesis of CLDI. Premature infants exhibit an immature response to oxidative stress [3], immature interleukin-10-mediated inflammatory responses [4,5], persistence of neutrophilic inflammation and an imbalance of a 1 -protease inhibitor activity [6]. Nitric oxide (NO) metabolism plays a crucial role in many of these inflammatory processes. Exhaled NO (eNO) is altered during both oxidative stress [7] and neutrophilic inflammation [8]. There is also increasing evidence that NO is involved in lung development and growth, as well as in angiogenesis [9,10]. Recently, it has been demonstrated that premature baboons, in which CLDI subsequently develops, show pre-existing alterations of NO metabolism at birth [11]. These animals have decreased levels of constitutive forms of NO synthase (endothelial nitr...

It is not known at what age lung function impairment may arise in children with cystic fibrosis (CF). We assessed lung function shortly after birth in infants with CF diagnosed by newborn screening.We performed infant lung function measurements in a prospective cohort of infants with CF and healthy controls. We assessed lung clearance index (LCI), functional residual capacity (FRC) and tidal breathing parameters. The primary outcome was prevalence and severity of abnormal lung function (±1.64 z-scores) in CF.We enrolled 53 infants with CF (mean age 7.8 weeks) and 57 controls (mean age 5.2 weeks). Compared to controls, LCI and FRC were elevated (mean difference 0.30, 95% CI 0.02-0.60; p=0.034 and 14.5 mL, 95% CI 7.7-21.3 mL; p<0.001, respectively), while ratio of time to peak tidal expiratory flow to expiratory time was decreased in infants with CF. In 22 (41.5%) infants with CF, either LCI or FRC exceeded 1.64 z-scores; three infants had both elevated LCI and FRC.Shortly after birth, abnormal lung function is prevalent in CF infants. Ventilation inhomogeneity or hyperinflation may serve as noninvasive markers to monitor CF lung disease and specific treatment effects, and could thus be used as outcome parameters for future intervention studies in this age group.

Markedly increased pulmonary blood flow because of a relevant atrial septal defect (ASD) leads to impaired cardiopulmonary function during maximum exercise in adults. No comparative preoperative and postoperative data are available on the short‐term effects of shunt closure on cardiorespiratory function at peak exercise in children. Pulmonary function testing at rest and cardiopulmonary exercise testing together with haemodynamic assessment was done prospectively in children with an ASD preoperatively and again after full recovery at 3–4 mo postoperatively and compared with a matched normal population. Sixteen children, aged 6.8–16.1 y, with a defect of 8–23 mm (median 15 mm) and a pulmonary/systemic flow ratio of 1.5–3.5 (median 2.2) were tested and compared with 15 healthy children. Preoperatively, baseline pulmonary function parameters and exercise capacity were no different from normals. At peak exercise, patients with a shunt had increased pulmonary resistance, especially of the distal airways (p= 0.04), with a significantly larger proportion of children having a paradoxical increase in total airway resistance during exercise (p < 0.05). Maximum serum lactate at peak exercise was elevated (p < 0.05) in patients. In patients, maximum oxygen uptake was impaired (p= 0.03) and remained so at repeat evaluation postoperatively. The same observation was made for chronotropic response to exercise. Conclusion: Cardiopulmonary exercise parameters in patients with ASD differed only slightly from those in normal children. The most important deviations were a lower maximum oxygen uptake and an increase in airway resistance at maximum exercise.

Primary ciliary dyskinesia (PCD) is a rare, hereditary, multiorgan disease caused by defects in the structure and function of motile cilia. It results in a wide range of clinical manifestations, most commonly in the upper and lower airways. Central data collection in national and international registries is essential to studying the epidemiology of rare diseases and filling in gaps in knowledge of diseases such as PCD. For this reason, the Swiss Primary Ciliary Dyskinesia Registry (CH-PCD) was founded in 2013 as a collaborative project between epidemiologists and adult and paediatric pulmonologists. We describe the objectives and methodology of the CH-PCD, present initial results, and give an overview of current and ongoing projects. The registry records patients of any age, suffering from PCD, who are treated and resident in Switzerland. It collects information from patients identified through physicians, diagnostic facilities and patient organisations. The registry dataset contains data on diagnostic evaluations, lung function, microbiology and imaging, symptoms, treatments and hospitalisations. By May 2018, CH-PCD has contacted 566 physicians of different specialties and identified 134 patients with PCD. At present, this number represents an overall 1 in 63,000 prevalence of people diagnosed with PCD in Switzerland. Prevalence differs by age and region; it is highest in children and adults younger than 30 years, and in Espace Mittelland. The median age of patients in the registry is 25 years (range 5–73), and 41 patients have a definite PCD diagnosis based on recent international guidelines. Data from CH-PCD are contributed to international collaborative studies and the registry facilitates patient identification for nested studies. CH-PCD has proven to be a valuable research tool that already has highlighted weaknesses in PCD clinical practice in Switzerland. Trial registration number NCT03606200