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Background: Progression of structural lung disease (SLD) is a major risk factor for morbidity in patients with cystic fibrosis (CF). We studied changes in SLD and correlations with spirometry and nitrogen multiple breath washout (N 2 MBW) outcomes to explore associations in contemporary evolution between structural and functional abnormalities in CF lung disease., Methods: Spirometry-controlled chest-CTs using PRAGMA-CF for scoring extent of SLD, spirometry, and N 2 MBW were performed at two-year intervals in school-age children with CF., Results: Fifty-seven children aged 6-18 years were included. No significant progression in mean PRAGMA-CF scores was observed. Half of the children showed improvement in the proportion of bronchiectasis (%Bx). Lung Clearance Index (LCI) and the second moment ratio (M2) increased significantly and baseline values correlated significantly with SLD at follow-up (p ≤ 0.0002). The correlation between the change in M2 (∆M2) and the change in total SLD was R = 0.27 (p = 0.048). We found high negative predictive values (100%) for ∆M2<10% to exclude progression in SLD. For stable or improving values of LCI and M2, the predicted probability for progression in SLD was 16% and 14%, respectively (upper 95% confidence limit: 33%). Evolution in N 2 MBW and CT outcomes was discordant in half of the children., Conclusions: We found no progression in SLD over 2 years in school-age children with CF, in contrast to both LCI and M2, which along with discordant outcomes in half of the children underlines that N 2 MBW and CT assess different aspects of CF lung disease. However, stable outcomes from N 2 MBW were associated with stable structural lung disease., Competing Interests: Declaration of Competing Interest None of the authors have financial relationships with any organizations that might have an interest in the submitted work., (Copyright © 2020 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Obstructive airway disease is nonuniformly distributed throughout the bronchial tree, although the extent to which this occurs can vary among conditions. The multiple-breath washout (MBW) test offers important insights into pediatric lung disease, not available through spirometry or resistance measurements. The European Respiratory Society/American Thoracic Society inert gas washout consensus statement led to the emergence of validated commercial equipment for the age group 6 years and above; specific recommendations for preschool children were beyond the scope of the document. Subsequently, the focus has shifted to MBW applications within preschool subjects (aged 2-6 yr), where a "window of opportunity" exists for early diagnosis of obstructive lung disease and intervention., Methods: This preschool-specific technical standards document was developed by an international group of experts, with expertise in both custom-built and commercial MBW equipment. A comprehensive review of published evidence was performed., Results: Recommendations were devised across areas that place specific age-related demands on MBW systems. Citing evidence where available in the literature, recommendations are made regarding procedures that should be used to achieve robust MBW results in the preschool age range. The present work also highlights the important unanswered questions that need to be addressed in future work., Conclusions: Consensus recommendations are outlined to direct interested groups of manufacturers, researchers, and clinicians in preschool device design, test performance, and data analysis for the MBW technique.

Rationale: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by progressive lung disease. Pseudomonas aeruginosa is a major pathogen in this disease and is known to impact lung function. Previous genotype–phenotype studies have been limited by cross-sectional designs, isolated adult or pediatric populations, small numbers, or short follow-up durations. Objectives: We aimed to explore long-term lung function in PCD grouped by genotypes and ultrastructural defects, considering the influence of P. aeruginosa. Methods: In this retrospective observational study, we analyzed 43 years of spirometry and 20 years of microbiology data. Using linear mixed-effects models, we estimated forced expiratory volume in 1 second z-score trends and compared them at ages 10, 25, and 50 years, whereas generalized estimating equations were used to assess P. aeruginosa prevalence between groups. In a secondary analysis, we matched spirometry and microbiology samples to evaluate the influence of P. aeruginosa on lung function. Results: We included 127 genotyped patients, 6,691 spirometry measurements, and 10,082 microbiology samples. CCDC39 and CCDC40 variants showed early-onset and sustained decline in lung function, whereas DNAH11 and HYDIN variants demonstrated relative stability. Lung function in the proximity of positive P. aeruginosa cultures was on average 0.06 z-score lower. Despite this, differences between groups remained largely unaffected by P. aeruginosa. Conclusions: Long-term lung function in PCD follows discrete genotype-specific profiles and appears independent of P. aeruginosa infection. We confirm and extend previous findings of CCDC39 and CCDC40 as variants associated with early-onset severe lung function impairment persisting in the long term. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) care in Denmark has been characterized by close monitoring and pre‐emptive treatment of lung disease and other CF‐related complications. Continuous evaluation through data collection and commitment to clinical research has incrementally improved outcomes. This approach has been in line with best practices set forth by European Standards of Care but has also gone beyond Society standards particularly pertaining to early treatment with high‐dose combination antimicrobial therapy. Despite a high prevalence of severe CF variants, lung function has been among the best in Europe. In this review, the Danish approach to management of CF prior to the introduction of new CF modulator treatment is explained and benchmarked. Downsides to the Danish approach are discussed and include increased burden of treatment, risk of antimicrobial resistance, side‐effects and costs. [ABSTRACT FROM AUTHOR]

Pulmonary chronic graft-versus-host disease (cGVHD) is a substantial cause of pulmonary morbidity and mortality post-haematopoietic stem cell transplantation (HSCT). Current spirometry-based monitoring strategies have significant limitations. Understanding the utility of novel peripheral airway function tests -- multiple breath washout (MBW) and oscillometry -- is critical in efforts to improve detection, facilitate earlier intervention and improve outcomes. In this scoping review, we identified 17 studies investigating MBW or oscillometry, or both, after allogenic HSCT. Despite small study numbers limiting the ability to draw firm conclusions, several themes were evident. Detectable peripheral airway abnormality in MBW occurred in a substantial proportion prior to HSCT. MBW indices post-HSCT were more frequently abnormal than spirometry when reporting group data and among those with extrapulmonary cGVHD and pulmonary cGVHD. Changes in MBW indices over time may be more indicative of pulmonary complications than absolute values at any given time point. Oscillometry indices were often normal at baseline, but more frequently abnormal in those who developed pulmonary cGVHD. Pooling currently available individual participant data across these studies may improve our ability to formally compare their respective sensitivity and specificity at specific time points and assess the trajectory of MBW and oscillometry indices over time. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) lung disease is characterized by increased ventilation inhomogeneity (VI), as measured by multiple-breath washout (MBW). Lung clearance index (LCI) is the most reported VI outcome. This study aimed to evaluate historically published reference equations for sulfur hexafluoride (SF6) MBW outcomes, to data collected using updated commercial SF6MBW equipment, and to produce device-specific equations if necessary. SF6MBW was performed in 327 healthy children aged 0.1–18.4 yr [151 (46%) girls], 191 (58.4%) <3 yr. z-Scores were calculated from published reference equations (FRC and LCI) and multivariate linear regression was performed to produce device-specific reference equations. Due to increasing residual standard deviations with increasing LCI values, investigation of methods for improvement were investigated, based on the relationship between VI and dead space ventilation (VD/VT; dead space volume/tidal volume) in a cohort of 59 healthy children, 26 children with CF (n = 138 test occasions), and 49 adults with lung disease. Historical SF6MBW reference equations were unsuitable for EXHALYZER D data. In contrast to LCI and log10(LCI), 1/LCI (ventilation distribution efficiency; VDE) was linearly related to VD/VT, with z-scores linearly related to its absolute values. Reference equations were reported for VDE and log10(FRC). Significant predictors for VDE and log10(FRC), respectively, were log10(age) and sex, and log10(height), sex, and posture. VDE is potentially a better index of VI than LCI, particularly in more advanced CF lung disease and also for longitudinal monitoring. Further confirmatory clinical studies, particularly longitudinal imaging studies of structural or ventilatory changes, are warranted. [ABSTRACT FROM AUTHOR]

The use of pulmonary function tests (PFTs) has been widely described in airway diseases like asthma and cystic fibrosis, but for children's interstitial lung disease (chILD), which encompasses a broad spectrum of pathologies, the usefulness of PFTs is still undetermined, despite widespread use in adult interstitial lung disease. A literature review was initiated by the COST/Enter chILD working group aiming to describe published studies, to identify gaps in knowledge and to propose future research goals in regard to spirometry, wholebody plethysmography, infant and pre-school PFTs, measurement of diffusing capacity, multiple breath washout and cardiopulmonary exercise tests in chILD. The search revealed a limited number of papers published in the past three decades, of which the majority were descriptive and did not report pulmonary function as the main outcome. PFTs may be useful in different stages of management of children with suspected or confirmed chILD, but the chILD spectrum is diverse and includes a heterogeneous patient group in all ages. Research studies in well-defined patient cohorts are needed to establish which PFT and outcomes are most relevant for diagnosis, evaluation of disease severity and course, and monitoring individual conditions both for improvement in clinical care and as end-points in future randomised controlled trials. [ABSTRACT FROM AUTHOR]

Primary ciliary dyskinesia (PCD) is an inherited ciliopathy leading to chronic suppurative lung disease, chronic rhinosinusitis, middle ear disease, sub-fertility and situs abnormalities. As PCD is rare, it is important that scientists and clinicians foster international collaborations to share expertise in order to provide the best possible diagnostic and management strategies. 'Better Experimental Approaches to Treat Primary Ciliary Dyskinesia' (BEAT-PCD) is a multidisciplinary network funded by EU COST Action (BM1407) to coordinate innovative basic science and clinical research from across the world to drive advances in the field. The fourth and final BEAT-PCD Conference and fifth PCD Training School were held jointly in March 2019 in Poznan, Poland. The varied program of plenaries, workshops, break-out sessions, oral and poster presentations were aimed to enhance the knowledge and skills of delegates, whilst also providing a collaborative platform to exchange ideas. In this final BEAT-PCD conference we were able to build upon programmes developed throughout the lifetime of the COST Action. These proceedings report on the conference, highlighting some of the successes of the BEAT-PCD programme. [ABSTRACT FROM AUTHOR]

Primary ciliary dyskinesia (PCD) is a rare heterogenous condition that causes progressive suppurative lung disease, chronic rhinosinusitis, chronic otitis media, infertility and abnormal situs. 'Better Experimental Approaches to Treat Primary Ciliary Dyskinesia' (BEAT-PCD) is a network of scientists and clinicians coordinating research from basic science through to clinical care with the intention of developing treatments and diagnostics that lead to improved long-term outcomes for patients. BEAT-PCD activities are supported by EU Framework Programme Horizon 2020 funded COST Action (BM1407). The Inaugural Conference of BEAT-PCD was held in December 2015 in Southampton, UK. The conference attracted ninety-six scientists, clinicians, allied health professionals, industrial partners and patient representatives from twenty countries. We aimed to identify the needs for PCD research and clinical care, particularly focussing on basic science, epidemiology, diagnostic testing, clinical management and clinical trials. The multidisciplinary conference provided an interactive platform for exchanging ideas through a program of lectures, poster presentations, breakout sessions and workshops. This allowed us to develop plans for collaborative studies. In this report, we summarize the meeting, highlight developments, and discuss open questions thereby documenting ongoing developments in the field of PCD research. [ABSTRACT FROM AUTHOR]

Rationale: The diffusing capacity (DL) of the lung can be divided into two components: the diffusing capacity of the alveolar membrane (Dm) and the pulmonary capillary volume (Vc). DL is traditionally measured using a single-breath method, involving inhalation of carbon monoxide, and a breath hold of 8–10 seconds (DL,CO). This method does not easily allow calculation of Dm and Vc. An alternative single-breath method (DL,CO,NO), involving simultaneous inhalation of carbon monoxide and nitric oxide, and traditionally a shorter breath hold, allows calculation of Dm and Vc and the DL,NO/DL,CO ratio in a single respiratory maneuver. The clinical utility of Dm, Vc, and DL,NO/DL,CO in the pediatric age range is currently unknown but also restricted by lack of reference values. Objectives: The aim of this study was to establish reference ranges for the outcomes of DL,CO,NO with a 5 second breath hold, including the calculated outcomes Dm, Vc, and the DL,NO/DL,CO ratio, as well as to establish reference values for the outcomes of the traditional DL,CO method, with a 10 second breath hold in children. Methods: DL,CO,NO and DL,CO were measured in healthy children, of European descent, aged 5–17 years using a Jaeger Masterscreen PFT. The data were analyzed using the Generalized Additive Models for Location Scale and Shape (GAMLSS) statistical method. Measurements and Main Results: A total of 326 children were eligible for diffusing capacity measurements, resulting in 312 measurements of DL,CO,NO and 297 of DL,CO, respectively. Reference equations were established for the outcomes of DL,CO,NO and DL,CO, including the calculated values: Vc, Dm, and the DL,NO/DL,CO ratio. Conclusion: These reference values are based on the largest sample of children to date and may provide a basis for future studies of their clinical utility in differentiating between alterations in the pulmonary circulation and changes in the alveolar membrane in pediatric patients. [ABSTRACT FROM AUTHOR]

Background: Commercial aircraft are pressurised to ~2438 m (8000 ft) above sea level that equates breathing 15% oxygen at sea level. A preflight hypoxic challenge test (HCT) is therefore recommended for children with cystic fibrosis or other chronic lung diseases and inflight oxygen is advised if pulse oximetric saturation (SpO2) decreases <90%. Objective: Study responses to a modified HCT, encompassing various body positions and light physical activity, reflecting relevant activities of children during flight, with a view to challenge the evidence of the current cut-off. Methods: Oxygenation, heart rate and ventilation were observed in 34 healthy schoolchildren (17 boys) undergoing a modified HCT, alternating between breathing room air and 15% oxygen in nitrogen while seated, supine, standing and walking at 3 km/h and 5 km/h. Results: Nadir SpO2 <90%, median (range), occurred in 9 subjects sitting, 89% (78-89%); 6 supine, 88.5% (87-89%); 9 standing, 89% (85-89%); 23 walking 3 km/h, 87% (74-89%); and 21 walking 5 km/h, 86% (74-89%). Total time <90% for these subjects in seconds was 20 (10-80) sitting, 30 (10-190) supine, 50 (10-150) standing, 80 (10-260) walking 3 km/h and 125 (10-300) walking 5 km/h. Light exercise in general led to lower SpO2: 91% (77-96%), p<0.0001. Conclusions: A modified HCT led to moments of desaturation below 90% in various body positions at rest and during light physical activity in healthy schoolchildren. It is questionable whether the international recommended cut-off of 90% for children with chronic lung disease reflects clinical oxygen dependence during flights. [ABSTRACT FROM AUTHOR]

Background The lung clearance index (LCI) derived from the multiple breath inert gas washout (MBW) test reflects global ventilation distribution inhomogeneity. It is more sensitive than forced expiratory volume in 1 s (FEV1) for detecting abnormal airway function and correlates closely with structural lung damage in children with cystic fibrosis, which shares features with primary ciliary dyskinesia (PCD). Normalised phase III slope indices Scond and Sacin reflect function of the small conducting and acinar airways, respectively. The involvement of the peripheral airways assessed by MBW tests has not been previously described in PCD. Methods A cross-sectional MBW study was performed in 27 children and adolescents with verified PCD, all clinically stable and able to perform lung function tests. LCI, Scond (n=23) and Sacin (n=23) were derived from MBW using a mass spectrometer and sulfur hexafluoride as inert marker gas. MBW indices were compared with present age, age at diagnosis and spirometry findings, and were related to published normative values. Results LCI, Scond and Sacin were abnormal in 85%, 96% and 78% of patients with PCD and in 81%, 93% and 79%, respectively, of 13/27 subjects with normal FEV1. LCI and Sacin correlated significantly while Scond did not correlate with any other lung function parameters. None of the lung function measurements correlated with age or age at diagnosis. Conclusions PCD is characterised by marked peripheral airway dysfunction. MBW seems promising in the early detection of lung damage, even in young patients with PCD. The relationship of MBW indices to the outcome of long-term disease and their role in the management of PCD need to be assessed. [ABSTRACT FROM AUTHOR]

The article presents a review on the method of measuring the specific airway resistance (sRaw), called plethysmographic measurements, in young children. The aim of this article is to promote a wider dissemination of measurement of sRaw in young children in research as well as in clinical practice. The simple principles of sRaw measurements was explained and provides a review on the data on the validity of the method in young children. In addition, it proposes a protocol for assessing sRaw.

Aim Methods Results Conclusions Knowledge about the clinical role that respiratory viruses play in infants and toddlers with cystic fibrosis (CF) remains limited. We determined the prevalence of respiratory viruses in routine respiratory secretion samples in children aged 0–3 years with CF. Associations with bacterial infections, respiratory tract symptoms and lung function were also explored.This prospective, longitudinal, single‐centre study added viral polymerase chain reaction detection to the routine monitoring of CF lung disease at Copenhagen University Hospital, Denmark, from 1 July 2019 to 31 August 2020. The existing programme included monthly clinical assessments with endo‐laryngeal suction for bacterial culturing and quarterly lung function testing.We studied 19 children (11 males) with a median age of 1.8 (range 0.11–2.99) years. Viruses were detected in 86/193 (45%) samples. Rhinoviruses and enteroviruses were the most common (88%), followed by adenoviruses (9%), parainfluenza 1–3 (6%) and the respiratory syncytial virus (5%). A positive association was found between the annual incidence of viruses and bacteria, but there was no correlation with respiratory tract symptoms or lung function.Respiratory viruses were commonly detected in routine respiratory secretion samples. However, the results from this small study did not justify specific conclusions. [ABSTRACT FROM AUTHOR]

• The impact of ETI treatment on exercise capacity measured by CPET in people with cystic fibrosis. • A prospective design and the inclusion of a considerable Danish cohort. • An increase in oxygen uptake among pwCF after one year of ETI treatment without any further intervention. • A significant outcome but it seems not to be clinically relevant. Cystic Fibrosis (CF) is an inherited multiorgan disease that causes lung damage and early death. People with CF (pwCF) experience diminished exercise capacity compared to the general population. This is due to an accelerated decline in lung function resulting from recurrent lung infections, declining lung function and nutritional challenges. Since 2020 the CFTR-modulator Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been approved for pwCF aged 12 and above in Denmark. Initial experiences with the medication have shown promising results, including improved lung function and disease stability. To date a limited number of studies have evaluated the impact of CFTR-modulators on exercise capacity in pwCF. The study aims to assess the impact of one year of ETI treatment, without any further intervention, on exercise capacity measured through cardiopulmonary exercise test (CPET) in pwCF aged 12 years and above. A Danish prospective registry cohort study including pwCF from CF-Center Copenhagen, Copenhagen University Hospital and CF-Center Aarhus, Aarhus University Hospital. Participants underwent CPET before initiating ETI and at follow up one year later. Primary outcomes were VO₂ peak (ml/kg/min), secondary outcomes were VO2 peak (ml/min), VO2 peak (% pred), watt-max, HR-max and saturation at max. The difference between baseline and follow-up was assessed using a paired-sample t -test and regression analyses were applied to relevant outcomes. We included 229 pwCF in the analyses. An increase in oxygen uptake, VO₂ peak (ml/kg/min) from baseline to follow-up was observed; 0.6, 95% CI [0.06; 1.09] p = 0.03. Moreover, significant increase was noted for all other CPET outcomes. Regression analysis showed that changes in FEV₁% pred and BMI could explain some of the differences, 0.05 ml/kg/min, 95% CI [0.01, 0.1] p = 0.02 and -0.5 ml/kg/min, 95% CI [-0.8, -0.2] p = 0.002 respectively. Among Danish pwCF we found a significant, but not clinically relevant, increase in oxygen uptake, after one year of ETI treatment. [ABSTRACT FROM AUTHOR]

Background: Lung resection is a controversial and understudied therapeutic modality in Primary Ciliary Dyskinesia (PCD). We assessed the prevalence of lung resection in PCD across countries and compared disease course in lobectomised and non-lobectomised patients.Methods: In the international iPCD cohort, we identified lobectomised and non-lobectomised age and sex-matched PCD patients and compared their characteristics, lung function and BMI cross-sectionally and longitudinally.Results: Among 2896 patients in the iPCD cohort, 163 from 20 centers (15 countries) underwent lung resection (5.6%). Among adult patients, prevalence of lung resection was 8.9%, demonstrating wide variation among countries. Compared to the rest of the iPCD cohort, lobectomised patients were more often females, older at diagnosis, and more often had situs solitus. In about half of the cases (45.6%) lung resection was performed before presentation to specialized PCD centers for diagnostic work-up. Compared to controls (n = 197), lobectomised patients had lower FVC z-scores (- 2.41 vs - 1.35, p = 0.0001) and FEV1 z-scores (- 2.79 vs - 1.99, p = 0.003) at their first post-lung resection assessment. After surgery, lung function continued to decline at a faster rate in lobectomised patients compared to controls (FVC z-score slope: - 0.037/year Vs - 0.009/year, p = 0.047 and FEV1 z-score slope: - 0.052/year Vs - 0.033/year, p = 0.235), although difference did not reach statistical significance for FEV1. Within cases, females and patients with multiple lobe resections had lower lung function.Conclusions: Prevalence of lung resection in PCD varies widely between countries, is often performed before PCD diagnosis and overall is more frequent in patients with delayed diagnosis. After lung resection, compared to controls most lobectomised patients have poorer and continuing decline of lung function despite lung resection. Further studies benefiting from prospective data collection are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

• A randomised, controlled pilot study in school-age children with cystic fibrosis. • One month's withdrawal of dornase alfa caused a significant increase in LCI. • Short-term discontinuation of dornase alfa may affect LCI values. • When using LCI as endpoint, dornase alfa adherence optimally needs to be addressed. The lung clearance index (LCI) is increasingly used as an outcome in clinical trials of patients with mild cystic fibrosis (CF) lung disease. Yet, understanding the impact of standard CF respiratory therapy on LCI is needed. We assessed to what degree withdrawal of nebulised dornase alfa affected LCI in school-age children with CF not receiving CFTR modulators or hydrator therapy. A single-centre, randomised, controlled, parallel group study to determine effects of one month's withdrawal of nebulised dornase alfa (intervention) in 5-18 years old children with CF. Remaining chronic maintenance therapy stayed unchanged. Outcome measures were assessed at two visits one month apart. Primary outcome was absolute change in LCI. Secondary outcomes were FEV 1 , FEF 25–75 and CF Questionnaire-revised (CFQ-R) respiratory symptom score. Possible harmful effects were assessed by comparing the occurrence of pulmonary exacerbations between groups. Twenty-eight children (median age 10.4 [interquartile range: 7.6; 13.5] years) with CF received standard care (n = 14) or intervention (n = 14). Compared with the control group, LCI increased (worsened) 1.74 (95% confidence interval: 0.62; 2.86) during withdrawal of dornase alfa, while FEV 1 (-6.8% predicted) and FEF 25–75 (-13.1% predicted) decreased significantly. Change in CFQ-R respiratory symptom score and the occurrence of pulmonary exacerbations did not differ significantly between groups. One month's withdrawal of dornase alfa caused increasing ventilation inhomogeneity and deteriorating FEV 1 and FEF 25–75 in school-age children with mild CF. Hence, adherence to dornase alfa optimally needs to be addressed when using LCI and spirometric parameters as endpoints, even in short-term clinical trials. [ABSTRACT FROM AUTHOR]

Abstract: Background: The quality of chest Computed Tomography (CT) images in children is dependent upon a sufficient breath hold during CT scanning. This study evaluates the influence of spirometric breath hold monitoring with biofeedback software on inspiratory and expiratory chest CT lung density measures, and on trapped air (TA) scoring in children with cystic fibrosis (CF). This is important because TA is an important component of early and progressive CF lung disease. Methods: A cross sectional comparison study was completed for chest CT imaging in two cohorts of CF children with comparable disease severity, using spirometric breath hold monitoring and biofeedback software (Copenhagen (COP)) or unmonitored breath hold manoeuvres (Gothenburg (GOT)). Inspiratory–expiratory lung density differences were calculated, and TA was scored to assess the difference between the two cohorts. Results: Eighty-four chest CTs were evaluated. Mean (95%CI) change in inspiratory–expiratory lung density differences was 436 Hounsfield Units (HU) (408 to 464) in the COP cohort with spirometric breath hold monitoring versus 229 HU (188 to 269) in the GOT cohort with unmonitored breath hold manoeuvres (p<0.0001). The Mean TA (95%CI) score was 6.93 (6.05 to 7.82) in COP patients and 3.81 (2.89 to 4.73) in GOT (p<0.0001) patients. Conclusions: In children with comparable CF lung disease, spirometric breath hold monitoring during examination yielded a large difference in lung volume between inhalation and exhalation, and allowed for a significantly greater measured change in lung density and TA score, compared to unmonitored breath hold maneuvers. This has implications to the clinical use of chest CT, especially in children with early CF lung disease. [Copyright &y& Elsevier]

Abstract: Background: We studied whether the sinuses might be foci for Pseudomonas aeruginosa lung infection. Methods: Endoscopic Sinus Surgery was performed in 78 CF patients; PFGE was used for bacterial genotyping. Material from sinuses and lungs were Gram-stained to detect biofilms. Immunoglobulins were measured in serum and saliva. Results: When P. aeruginosa was cultured simultaneously from the sinuses and the lungs they were genetically identical in 38 of the 40 patients (95%). In the sinuses, P. aeruginosa formed biofilms with minimal cellular inflammation, probably because of a significantly higher local production of secretory IgA compared with IgG (p <0.001). Conclusions: We have shown that P. aeruginosa form biofilm in the sinuses, which constitute an important bacterial reservoir for subsequent lung infection. The high amount of IgA in the upper airways probably protects P. aeruginosa from the inflammatory immune system, and they can proceed unnoticed into a permanent infectious focus that cannot be eradicated with antibiotics. [Copyright &y& Elsevier]