Inert gas washout tests, performed using the single- or multiple-breath washout technique, were first described over 60 years ago. As measures of ventilation distribution inhomogeneity, they offer complementary information to standard lung function tests, such as spirometry, as well as improved feasibility across wider age ranges and improved sensitivity in the detection of early lung damage. These benefits have led to a resurgence of interest in these techniques from manufacturers, clinicians and researchers, yet detailed guidelines for washout equipment specifications, test performance and analysis are lacking. This manuscript provides recommendations about these aspects, applicable to both the paediatric and adult testing environment, whilst outlining the important principles that are essential for the reader to understand. These recommendations are evidence based, where possible, but in many places represent expert opinion from a working group with a large collective experience in the techniques discussed.Finally, the important issues that remain unanswered are highlighted. By addressing these important issues and directing future research, the hope is to facilitate the incorporation of these promising tests into routine clinical practice.

The diagnosis of primary ciliary dyskinesia is often confirmed with standard, albeit complex and expensive, tests. In many cases, however, the diagnosis remains difficult despite the array of sophisticated diagnostic tests. There is no “gold standard” reference test. Hence, a Task Force supported by the European Respiratory Society has developed this guideline to provide evidence-based recommendations on diagnostic testing, especially in light of new developments in such tests, and the need for robust diagnoses of patients who might enter randomised controlled trials of treatments. The guideline is based on pre-defined questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. It focuses on clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence. It then used a modified Delphi survey to develop an algorithm for the use of diagnostic tests to definitively confirm and exclude the diagnosis of primary ciliary dyskinesia; and to provide advice when the diagnosis was not conclusive. Finally, this guideline proposes a set of quality criteria for future research on the validity of diagnostic methods for primary ciliary dyskinesia.

OBJECTIVE: Neonatal sepsis causes high mortality and morbidity in preterm infants, but less is known regarding the long-term outcome after sepsis. This study aimed to determine the impact of sepsis on neurodevelopment at 2 years9 corrected age in extremely preterm infants. PATIENTS AND METHODS: This was a multicenter Swiss cohort study on infants born between 2000 and 2007 at 24$\raisebox{1ex}{$0$}\!\left/ \!\raisebox{-1ex}{$7$}\right.$ to 27$\raisebox{1ex}{$6$}\!\left/ \!\raisebox{-1ex}{$7$}\right.$ weeks9 gestational age. Neurodevelopmental outcome was assessed with the Bayley Scales of Infant Development–II. Neurodevelopmental impairment (NDI) was defined as a Mental or Psychomotor Developmental Index lower than 70, cerebral palsy (CP), or visual or auditory impairment. RESULTS: Of 541 infants, 136 (25%) had proven sepsis, 169 (31%) had suspected sepsis, and 236 (44%) had no signs of infection. CP occurred in 14 of 136 (10%) infants with proven sepsis compared with 10 of 236 (4%) uninfected infants (odds ratio [OR]: 2.90 [95% confidence interval (CI): 1.22–6.89]; P = .016). NDI occurred in 46 of 134 (34%) infants with proven sepsis compared with 55 of 235 (23%) uninfected infants (OR: 1.85 [95% CI: 1.12–3.05]; P = .016). Multivariable analysis confirmed that proven sepsis independently increased the risk of CP (OR: 3.23 [95% CI: 1.23–8.48]; P = .017) and NDI (OR: 1.69 [95% CI: 0.96–2.98]; P = .067). In contrast, suspected sepsis was not associated with neurodevelopmental outcome (P > .05). The presence of bronchopulmonary dysplasia, pathologic brain ultrasonography, retinopathy, and sepsis predicted the risk of NDI (P < .0001). CONCLUSIONS: Proven sepsis significantly contributes to NDI in extremely preterm infants, independent of other risk factors. Better strategies aimed at reducing the incidence of sepsis in this highly vulnerable population are needed.

The airways of cystic fibrosis (CF) patients are characterised by neutrophils that release high amounts of elastase overwhelming the local antiprotease shield. Inhalation of α₁-antitrypsin (AAT) may restore the protease–antiprotease balance and attenuate airway inflammation in CF airways. The aims of the present study were: 1) to assess the best deposition region for inhaled AAT by two different inhalation strategies; and 2) to examine the effect of 4 weeks of AAT inhalation on lung function, protease–antiprotease balance and airway inflammation in CF patients.In a prospective, randomised study, 52 CF patients received a daily deposition by inhalation of 25 mg AAT for 4 weeks targeting their peripheral or bronchial compartment. The levels of elastase activity, AAT, pro-inflammatory cytokines, neutrophils, immunoglobulin G fragments and the numbers ofPseudomonas aeruginosawere assessed in induced sputum before and after the inhalation period.Inhalation of AAT increased AAT levels and decreased the levels of elastase activity, neutrophils, pro-inflammatory cytokines and the numbers ofP. aeruginosa. However, it had no effect on lung function. No difference was found between the peripheral and bronchial inhalation mode.In conclusion, although no effect on lung function was observed, the clear reduction of airway inflammation after α₁-antitrypsin treatment may precede pulmonary structural changes. The α₁-antitrypsin deposition region may play a minor role for α₁-antitrypsin inhalation in cystic fibrosis patients.

Post-natal exposure to air pollution is associated with diminished lung growth during school age. The current authors aimed to determine whether pre-natal exposure to air pollution is associated with lung function changes in the newborn.In a prospective birth cohort of 241 healthy term-born neonates, tidal breathing, lung volume, ventilation inhomogeneity and exhaled nitric oxide (eNO) were measured during unsedated sleep at age 5 weeks. Maternal exposure to particles with a 50% cut-off aerodynamic diameter of 10 μm (PM₁₀), nitrogen dioxide (NO₂) and ozone (O₃), and distance to major roads were estimated during pregnancy. The association between these exposures and lung function was assessed using linear regression.Minute ventilation was higher in infants with higher pre-natal PM₁₀exposure (24.9 mL·min⁻¹per μg·m⁻³PM₁₀). The eNO was increased in infants with higher pre-natal NO₂exposure (0.98 ppb per μg·m⁻³NO₂). Post-natal exposure to air pollution did not modify these findings. No association was found for pre-natal exposure to O₃and lung function parameters.The present results suggest that pre-natal exposure to air pollution might be associated with higher respiratory need and airway inflammation in newborns. Such alterations during early lung development may be important regarding long-term respiratory morbidity.