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Abstract: Background: Risk factors for methicillin-resistant Staphylococcus aureus (MRSA) in Cystic Fibrosis (CF) and the impact on CF disease progression are still under debate. The objectives of this study were to determine clinical variables associated with MRSA colonization and examine impact on FEV1 evolution in CF patients. Methods: A retrospective case–control study using the University Hospital of Brussels CF clinic patient registry from 2002 to 2010, comparing clinical variables and decline of FEV1 of MRSA positive patients with age and sex matched controls, chronically colonized with S. aureus. Results: Thirty of the 165 CF patients, chronically colonized with S. aureus, had cultures positive for MRSA (18.2%). Excluding patients under 4years, the prevalence became 15.2% (23/151). Chronic colonization (i.e., three or more consecutive positive cultures) was found in 19/151 (12.6%). The MRSA positive group showed a higher proportion of patients with genotype F508del, less pancreas sufficient patients, more bronchiectasis and more frequent hospitalization. The FEV1 recorded one year prior to, and at the moment of MRSA acquisition, was lower but not significantly different from that obtained in controls (72.9%±26.6 vs 84.3±21.8 and 68.2%±27.1 vs 81.4%±24.3 respectively, p>0.1). However, FEV1 decline over 2- and 6-year periods, were significantly greater in the chronic MRSA group than in the controls (−5%±5.5 vs −2.5±2.3 over 2years (p=0.043) and −1.8%±4.6 vs −1.0%±1.9 over a 6-year period (p=0.026)). Conclusion: In our center the prevalence of MRSA in CF patients, chronically colonized with S. aureus and over the age of 4years, was 15.2% (12.6% chronic infection). MRSA colonization was shown to be associated with a genotype F508del, presence of bronchiectasis and hospitalization. Our spirometric data also show that a MRSA episode entails an FEV1 decline that is almost double that predicted for CF patients who can remain unaffected by MRSA. [Copyright &y& Elsevier]

Background: Legionnaires' Disease (LD) rarely evolves into pulmonary abscesses. The current systematic review has been designed to explore therapeutical strategies in pulmonary cavitary LD., Methods: A research strategy was developed and applied to the databases Embase, Pubmed, and Web of Science from the 1st of January 2000 to the 1st of November 2022. Original articles, case series, case reports, and guidelines written in English, French, German, Italian, and Dutch were considered. Furthermore, medical records of patients treated at the University Hospital UZ Brussel for LD cavitary pneumonia, between the 1st of January 2016 to the 1st of January 2022, were reviewed., Results: Two patients were found by the UZ Brussel's medical records investigation. Through the literature review, 23 reports describing 29 patients, and seven guidelines were identified. The overall evidence level was low., Result of Synthesis (case Reports): The median age was 48 years and 65% were male. A polymicrobial infection was detected in 11 patients (44%) with other aerobic bacteria being the most commonly found. At diagnosis, 52% of patients received combination therapy, and fluoroquinolones were the preferred antimicrobial class. Anaerobic coverage was neglected in 33% of patients., Result of Synthesis (guidelines): Three guidelines favor monotherapy with fluoroquinolones or macrolides, while one suggested an antimicrobial combination in case of severe LD. Four guidelines recommended anaerobic coverage in case of lung abscesses., Conclusion: To date, the evidence supporting cavitary LD treatment is low. Monotherapy lowers toxicity and might be as effective as combination therapy. Finally, anaerobes should not be neglected., (© 2023. The Author(s).)

Background: To examine safety and efficacy of tezacaftor-ivacaftor (TEZ/IVA) in a real-life setting in adults living with cystic fibrosis., Methods: A multicentre retrospective observational study, including adults living with cystic fibrosis (pwCF) eligible for TEZ/IVA, with assessments at baseline, 3 months (visit 3mo ) and 6 months (visit 6mo ) after start of treatment. Outcomes included change in FEV 1 , LCI, FeNO, CFQ-R, estimated number of annual acute exacerbations, BMI, dosage of pancreatic enzyme replacement therapy (PERT) and airway microbiology. We also assessed safety., Results: Forty-eight adult pwCF (mean (±SD) age 33 (±12) years; mean FEV 1 65 (±19) %P) were included. Three subgroups were identified: pwCF F/F CFTR modulator-naive (n = 28; 58%), pwCF F/F previously treated with lumacaftor-ivacaftor (n = 11; 23%) and pwCF F/RF (n = 9; 19%). Adverse events were described in 3 pwCF (6%) during the 6-month observation period (in one leading to treatment interruption). At visit 3mo, FEV 1 had improved in all subgroups. In the entire group, mean FEV 1 had increased from 66 (±2.9) %P to 72 (±2.9) %P (p < 0.0001). Similarly, LCI improved by approximately one unit at visit 3mo (p = 0.02). At visit 6mo mean annual acute exacerbation rate decreased significantly (p = 0.02). Only in the CFQ-R social functioning domain score, a significant improvement was observed at visit 6mo (p < 0.01)., Conclusions: We showed that TEZ/IVA is safe, well tolerated and effective in terms of improvement of lung function, ventilation inhomogeneity, health-related social functioning, and reduction of estimated annual acute exacerbation rate, in adult pwCF F/F and F/RF. Results in this real-life study reflect those observed in RCTs.

Background: Few studies have investigated the collaborative potential between artificial intelligence (AI) and pulmonologists for diagnosing pulmonary disease. We hypothesised that the collaboration between a pulmonologist and AI with explanations (explainable AI (XAI)) is superior in diagnostic interpretation of pulmonary function tests (PFTs) than the pulmonologist without support., Methods: The study was conducted in two phases, a monocentre study (phase 1) and a multicentre intervention study (phase 2). Each phase utilised two different sets of 24 PFT reports of patients with a clinically validated gold standard diagnosis. Each PFT was interpreted without (control) and with XAI's suggestions (intervention). Pulmonologists provided a differential diagnosis consisting of a preferential diagnosis and optionally up to three additional diagnoses. The primary end-point compared accuracy of preferential and additional diagnoses between control and intervention. Secondary end-points were the number of diagnoses in differential diagnosis, diagnostic confidence and inter-rater agreement. We also analysed how XAI influenced pulmonologists' decisions., Results: In phase 1 (n=16 pulmonologists), mean preferential and differential diagnostic accuracy significantly increased by 10.4% and 9.4%, respectively, between control and intervention (p<0.001). Improvements were somewhat lower but highly significant (p<0.0001) in phase 2 (5.4% and 8.7%, respectively; n=62 pulmonologists). In both phases, the number of diagnoses in the differential diagnosis did not reduce, but diagnostic confidence and inter-rater agreement significantly increased during intervention. Pulmonologists updated their decisions with XAI's feedback and consistently improved their baseline performance if AI provided correct predictions., Conclusion: A collaboration between a pulmonologist and XAI is better at interpreting PFTs than individual pulmonologists reading without XAI support or XAI alone., Competing Interests: Conflict of interest: N. Das holds a patent on automated quality control of spirometry. E. Derom reports consultancy fees from Chiesi, GlaxoSmithKline, AstraZeneca and Boehringer Ingelheim. G. Brusselle reports payment or honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Sanofi. F. Burgos reports consultancy fees from Medical Graphics Corporation Diagnostics. M. Contoli reports grants from the University of Ferrara, Chiesi and GlaxoSmithKline, consultancy fees and honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Novartis, as well as support for attending meetings from Chiesi, AstraZeneca, GlaxoSmithKline and ALK-Abelló. W.D-C. Man is part funded by a NIHR Artificial Intelligence Award, and reports grants from the NIHR and British Lung Foundation, as well as honoraria from Mundipharma, Novartis, European Conference and Incentive Services DMC; and is the Honorary President of the Association for Respiratory Technology and Physiology (ARTP, UK). J.K. Quint reports grants from the MRC, HDR UK, GlaxoSmithKline, AstraZeneca and Chiesi, and consultancy fees from Insmed and Evidera. E. Vanderhelst reports grants from Chiesi, and consultancy fees and honoraria from Boehringer Ingelheim, Vertex and GlaxoSmithKline. M. Topalovic is part funded by a NIHR Artificial Intelligence Award, and is co-founder and shareholder of ArtiQ. W. Janssens reports grants from Chiesi and AstraZeneca, consultancy and lecture fees from AstraZeneca, Chiesi and GlaxoSmithKline, and he is co-founder and shareholder of ArtiQ. The remaining authors report no potential conflicts of interest., (Copyright ©The authors 2023.)

Objectives: Prevalence of MRSA in patients with CF has risen over the past decades, and chronic infection with MRSA is associated with worse outcome in this patient group., Methods: This retrospective observational study investigated long-term eradication rate in pediatric and adult CF patients with chronic MRSA infection, using a 6-month eradication regimen containing 2 oral antibiotics, combined with topical decolonisation measures. Respiratory tract cultures were performed at least every three months, from the first MRSA-positive culture onwards., Results: A total of 24 patients with chronic MRSA infection were identified from our CF patient registry, of which 13 patients underwent an eradication attempt. The regimen consisted of 2 oral antibiotics: a combination of rifampicin, fusidic acid, clindamycin and co-trimoxazol, based on the sensitivity pattern of the MRSA strain. At the end of the study period (median 8.2 years), 12 out of 13 patients (92%) were MRSA negative. None of the patients interrupted treatment due to side-effects., Conclusions: Eradication of chronic MRSA infection is feasible, well-tolerated and highly successful, and can offer a long-lasting MRSA-negative status, obviating the need for patient segregation.

Objectives: Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and high symptom burden that interferes with physical activity and results in a vicious cycle of inactivity and symptom worsening. The aim of this multicenter, observational study was to determine the prevalence and severity of morning, daytime and night-time symptoms as well as patterns of physical activity levels (PALs) and their interrelation in Belgian COPD patients, enrolled in the multinational SPACE study (NCT03031769)., Methods: Socio-demographic, socio-economic and disease characteristics data were collected from patients' medical records as part of a routine visit to their primary care practice or pulmonologist. Dedicated questionnaires were used to evaluate respiratory symptoms for each part of the day. PAL was assessed by means of self- and interview-reported tools, and physician's judgment. Patients were also classified according to GOLD recommendations 2013 and 2017., Results: Overall, 102 Belgian patients participated in the study (mean age 67 years, 60.8% males). Over 85% of patients experienced respiratory symptoms throughout the day and about one-third were considered as 'active' (PAL ≥150 minutes/week). Physician-assessed PALs were higher than self-reported PALs, categorizing fewer patients as 'inactive' (17.6% versus 42.2%, respectively). PALs and symptoms were weakly interrelated. Inactive patients were present in all GOLD classification groups., Conclusion: Stable Belgian COPD patients enrolled in the SPACE study presented 24-hour respiratory symptoms and insufficient PALs. Physicians tended to overestimate patients' physical activity. Inactive patients were present across all GOLD classification groups. New approaches are deemed necessary to objectively identify and activate sedentary patients.

Background and Objectives: Azithromycin was rapidly adopted as a repurposed drug to treat coronavirus disease 2019 (COVID-19) early in the pandemic. We aimed to evaluate its efficacy in patients hospitalised for COVID-19., Methods: In a series of randomised, open-label, phase 2 proof-of-concept, multicentre clinical trials (Direct Antivirals Working against the novel coronavirus (DAWn)), several treatments were compared with standard of care. In 15 Belgian hospitals, patients hospitalised with moderate to severe COVID-19 were allocated 2:1 to receive standard of care plus azithromycin or standard of care alone. The primary outcome was time to live discharge or sustained clinical improvement, defined as a two-point improvement on the World Health Organization (WHO) ordinal scale sustained for at least 3 days., Results: Patients were included between April 22 and December 17, 2020. When 15-day follow-up data were available for 160 patients (56% of preset cohort), an interim analysis was performed at request of the independent Data Safety and Monitoring Board. Subsequently, DAWn-AZITHRO was stopped for futility. In total, 121 patients were allocated to the treatment arm and 64 patients to the standard-of-care arm. We found no effect of azithromycin on the primary outcome with a hazard ratio of 1.044 (95% CI 0.772-1.413; p=0.7798). None of the predefined subgroups showed significant interaction as covariates in the Fine-Gray regression analysis. No benefit of azithromycin was found on any of the short- and longer-term secondary outcomes., Conclusion: Time to clinical improvement is not influenced by azithromycin in patients hospitalised with moderate to severe COVID-19., Competing Interests: The DAWn-AZITHRO investigators: T. Van Assche, T. Devos, G. Meyfroidt, H. Ceunen, B. Debaveye, M. ‘t Lam, K. Haesendonck, L. Goegebeur, J. Neyts, E. Van Wijngaerden and P. De Munter. Conflict of interest: I. Gyselinck declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: L. Liesenborghs declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: A. Belmans declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: M.M. Engelen declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: A. Betrains declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: Q. Van Thillo declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: P.A.H. Nguyen declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: P. Goeminne declares payment or honoraria for lectures from AstraZeneca, GlaxoSmithKline and Chiesi, and advisory board participation for Chiesi and GlaxoSmithKline, all in the 26 months prior to manuscript submission; in addition they declare the following unpaid roles: EMBARC board member; BeRS board member; ERS group 10 board member. Conflict of interest: A-C. Soenen declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: N. De Maeyer declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: C. Pilette declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: E. Papleux declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: E. Vanderhelst declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: A. Derweduwen declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: P. Alexander declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: B. Bouckaert declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: J-B. Martinot declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: L. Decoster declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: K. Vandeurzen declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: R. Schildermans declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: P. Verhamme declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: W. Janssens declares participation on an advisory board on antiretrovirals for Gilead Sciences in 2018, and support for attending meetings from Gilead Sciences (EACS 2019) and Sanofi Pasteur (ISTM 2019); in addition, they were secretary of the Belgische Vereniging voor Infectiologie en Klinische Microbiologie until 2020. Conflict of interest: R. Vos declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven., (Copyright ©The authors 2022.)

Despite being an important patient group, adult cystic fibrosis patients with an FEV 1 below 40%predicted have been excluded from clinical trials with elexacaftor/tezacaftor/ivacaftor. We conducted a real-life 3 months follow-up study in 14 adult CF patients (median FEV 1 34%predicted) demonstrating significant treatment effects in terms of FEV 1 (an increase of 12%predicted at 4 weeks, remaining stable thereafter). Corresponding decreases in lung clearance index LCI (by 31%predicted, down from baseline 247%predicted) and ventilation heterogeneity in the acinar compartment (Sacin) (by 411%predicted, down from baseline 798%predicted) suggest a distinct peripheral lung effect. One patient had intermittent treatment interruptions because of drug-induced liver injury. Our real-life data confirm that treatment with elexacaftor/tezacaftor/ivacaftor is effective in severely obstructive patients, and this is the first study to show time evolution of ventilation distribution improvement, pointing to the peripheral lung as the main site of treatment effect., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

We present the case of a 45-year-old woman, working as a silver polisher since 11 years, complaining of dyspnea on exertion and dry cough. Intensive diagnostic workup, including high-resolution CT scan of the chest and lung biopsy by VATS led to the diagnosis of pulmonary siderosis. Pulmonary siderosis is a benign, non-fibrotic type of pneumoconiosis caused by inhalation of iron oxide, which is generally asymptomatic (except in concurrent smoking or concurrent silicosis). Combination of relevant exposure and the typical findings on CT-imaging (centrilobular nodules without cranio-caudal gradient) usually strongly suggest the diagnosis, but this should always be discussed at a multidisciplinary consultation. This includes discussing whether to perform a lung biopsy for histological confirmation. Cessation of the causative exposure is the only-treatment one can take and then radiological features can improve and even disappear of time. Unfortunately, this treatment has an enormous impact on patient's life because it implies changing profession. Preventive measures can be taken by employers (respiratory equipment and ventilation). This case illustrates that physicians should stay vigilant about occupational exposures in clinical practice as well as the need for multidisciplinary consult in patients suspected of having interstitial lung disease.

Competing Interests: Conflict of interest Stylemans Dimitri, Vincken Stefanie and Vanderhelst Eef have participated in multiple randomized controlled trials with different CFTR modulators from Vertex, Abbvie and Proteostatis as subinvestigator or investigator.

Introduction: Most post COVID-19 follow-up studies are limited to a follow-up of 3 months. Whether a favorable evolution in lung function and/or radiological abnormalities is to be expected beyond 3 months is uncertain., Materials and Methods: We conducted a real-life follow-up study assessing the evolution in lung function, chest CT and ventilation distribution between 10 weeks and 6 months after diagnosis of COVID-19 pneumonia., Results: Seventy-nine patients were assessed at 6 months of whom 63 had chest CT at both follow-up visits and 46 had multiple breath washout testing to obtain lung clearance index (LCI). The study group was divided into a restrictive (n = 39) and a non-restrictive subgroup (n = 40) based on TLC z-score. Restriction was associated with a history of intubation, neuromuscular blockade use and critical illness polyneuropathy. Restriction significantly improved over time, but was not resolved by 6 months (median TLC z-score of -2.2 [IQR: -2.7; -1.5] at 6 months versus -2.7 [IQR: -3.1; -2.1] at 10 weeks). LCI did not evolve between both follow-up visits. Symptoms and chest CT score improved irrespective of restriction., Conclusion: We observed a disconnect between the improvement of COVID-19 related symptoms, chest CT lesions, and corresponding lung function. While CT imaging is almost normalized at 6 months, a further reduction of pulmonary restriction may be hoped for beyond 6 months in those patients showing restriction at their first follow-up visit., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Since studies about clinical status after COVID-19 are scarce, we conducted a cross sectional study with assessment of residual symptoms, lung function and chest CT., Materials and Methods: During an outpatient follow-up visit, chest CT, pulmonary function and COVID-19 related symptoms were assessed approximately 10 weeks after diagnosis. Demographics, baseline (time of diagnosis) CT score and blood results were collected from patient files. Association between lung function and clinical characteristics (baseline), blood markers (baseline), chest CT (baseline and follow-up) and symptom score (followup) was analysed. Mann-Whitney U tests and Chi squared tests were used for statistical comparison between subgroups with and without restriction., Results and Discussion: Two hundred-twenty subjects were evaluated at a median follow-up of 74±12 (SD) days. Median symptom and median CT score at follow-up were 1(IQR=0- 2) and 2(IQR=0-6) respectively. Forty-six percent of patients had normal lung function, while TLC and TLCO below the lower limit of normal were observed in 38% and 22% of subjects respectively. This restrictive pulmonary impairment was associated with length of hospital stay (8 vs 6 days; p=0.003), admission to the intensive care unit (27% vs 13%;p=0.009), and invasive mechanical ventilation (10% vs 0.7%;p=0.001), but not with symptom score or CT score at baseline and follow-up., Conclusions: Fifty-four percent of COVID-19 survivors had abnormal lung function 10 weeks after diagnosis. Restriction was the most prevalent pulmonary function, with the more critically ill patients being more prone to this condition. Yet, restriction could not be linked with abnormal imaging results or residual symptoms., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Smoking-induced ventilation heterogeneity measured at the mouth via established washout indices [lung clearance index (LCI) and alveolar mixing efficiency (AME)] potentially results from unequal expansion, which can be quantified by computer tomography (CT), and structural changes down to the lung periphery, characterized by CT parametric response mapping indices [percentage of lung affected by functional small airway disease (PRM fSAD ) and emphysema (PRM Emph )]. By combining CT imaging and nitrogen (N 2 ) washout tests in smokers, we specifically examined the roles of unequal lung expansion and peripheral structure. We first extracted three-dimensional maps of local lung expansion from registered inspiratory/expiratory CT images in 50 smokers (GOLD 0-IV) to compute for each smoker the theoretical N 2 washout concentration curve solely attributable to unequal local expansion. By a head-on comparison with washout N 2 concentrations measured at the mouth in the same smokers supine, we observed that 1 ) LCI increased from 4.8 ± 0.2 (SD) to 6.6 ± 0.8 (SD) due to unequal lung expansion alone and further increased to 9.0 ± 1.5 (SD) independent of local expansion and 2 ) AME decreased (from 100% by definition) to 95 ± 2 (SD)% due to unequal expansion alone and further decreased to 75 ± 7(SD)% independent of local expansion. In a multiple regression between the washout indices and CT-derived PRM fSAD and PRM Emph , LCI was related to PRM fSAD ( r  = +0.58; P < 0.001), whereas AME was related to both PRM fSAD ( r partial  = -0.44; P = 0.002) and PRM Emph ( r partial  = -0.31; P = 0.033), in line with AME being dominated by alterations in peripheral structure. We conclude that smokers showing an increased LCI without corresponding AME decrease are predominantly affected by unequal lung expansion, whereas an AME decrease with a commensurate LCI increase indicates a smoking-induced alteration of peripheral structure. NEW & NOTEWORTHY A head-on comparison between imaging and multiple breath washout in supine smokers shows that computer tomography-measured unequal local lung expansion accounts for 50% or less of smoking-induced increase in ventilation heterogeneity. The contributions from unequal lung expansion and peripheral structure to the two main washout indices also explain their respective association with parametric response mapping indices.

Background: Blood eosinophil counts (BEC) were recently included in the 2019 Global Initiative for Obstructive Lung Disease (GOLD) guideline as an easily accessible theragnostic biomarker for Chronic Obstructive Pulmonary Disease (COPD). However, the stability of BEC remains insufficiently studied., Methods: We conducted a retrospective study in six primary care practices in Belgium on data from Electronic Health Records of stable COPD patients, to characterise the stability of blood eosinophils over time. We report the percentage of patients with BEC persistently below or above the 2019 GOLD guideline thresholds (100 and 300 cells/μL). For each patient the mean, standard deviation (SD) and relative standard deviation (RSD) of the BEC were calculated to determine the intra-patient variability., Results: Ninety-eight patients were included, yielding 1082 eosinophil measurements (median 8 measurements/patient), with BEC ranging between 0 and 1504 cells/μL. Four (4.1%) patients had BEC persistently below 100 cells/μL, 34 (34.7%) had measurements persistently above this threshold. Approximately half of the patients (51.0%) had BEC persistently below 300 cells/μL and 3 (3.1%) patients had counts persistently above this threshold. 28.6% of patients crossed both threshold values throughout the registration period. The mean BEC per patient ranged between 15 and 846 cells/μL with an intra-patient SD between 5 and 658 cells/μL. The mean intra-patient RSD was 0.46. There was a significant strong positive correlation (Pearson analyses) between the mean BEC and SD (r = 0.765; n = 98). Simple linear regression was used to further describe the influence of the mean eosinophil count on the SD (B = 0.500; 95%CI 0.415-0.586; n = 98; p < 0.001)., Conclusion: BEC can be variable in individual COPD patients. Therefore, the use of a single measurement to guide therapeutic decisions remains debatable. Further prospective research remains necessary to validate the reproducibility of this biomarker.

Background : While cystic fibrosis (CF) lung disease is generally considered to be an obstructive disorder, other pulmonary function patterns (PFP) may occur. Furthermore, little is known about possible associations between PFP and genotype or phenotypical characteristics. Methods : Cross-sectional study including CF patients aged 16 years or more, identifying different PFP and exploring associations between PFP and genotype or phenotypical characteristics. Results : Obstructive PFP was most prevalent in our population (n = 80), comprising obstructive lung disease (62.5%), small airway (obstructive) disease (11.2%), and mixed obstructive-restrictive disorder (1.3%). However, one in four adult CF patients did not show any obstruction at all: normal (13.7%) or restrictive (8.8%) lung disease and isolated diffusion disorder (2.5%). Obstructive PFP was associated with a greater proportion of CF-related diabetes mellitus (CFRD) ( P  = 0.04), Pseudomonas aeruginosa colonization ( P  = 0.02) and frequent exacerbators ( P  = 0.04). We observed no association between PFP and genotype. Conclusions : Obstructive PFP remains the most common pulmonary function pattern in adult CF and is associated with CFRD, Pseudomonas aeruginosa colonization and frequent exacerbators.

Effective microbiogical eradication of methicillin-resistant Staphylococcus aureus (MRSA) in patients with cystic fibrosis (CF) can be obtained, but its effect is not always clear-cut in terms of spirometric indices. The aim of this observational prospective cohort study was to study the potential effect of eradication of chronic MRSA infection on lung function including ventilation distribution. Six CF patients, chronically colonized with MRSA (median age: 21 years (range 14-46); median FEV1: 76 (95%CI 58-98)%pred) were successfully eradicated using oral rifampicin and fusidic acid in combination with topical decolonization measures. Lung function and multiple breath washout test were performed at the start and at the end of the eradication protocol and after an average follow-up period of 7·5±1·5(SD) months. One patient cultured MRSA again 4 months after successful eradication. All patients reported reduced sputum production and viscosity. By the end of the follow-up period, there was an increase in ventilated FRCMBW and no change in plethysmographic FRCPL. This resulted in a significant decrease of trapped air by half a litre (from 579 to 40 ml; P = 0·013). Lung clearance index (LCI) also showed a small but significant decrease (from 7·2 to 6·7; P = 0·014) after eradication of MRSA. We conclude that MRSA eradication can be successful, also in terms of recruitment of previously unventilated air spaces, potentially due to reduced sputum production and/or viscosity.

Background: Chronic airway infection with methicillin-resistant Staphylococcus aureus (MRSA) in patients with cystic fibrosis (CF) is an increasing clinical problem, and therapeutic options are limited. Because chronic infection with MRSA can be associated with accelerated decline in lung function, eradication of MRSA is attempted in most CF centres today. The aim of this observational prospective cohort study was to determine whether it is possible to eradicate MRSA from airways of CF patients using prolonged oral antibiotic combination therapy together with topical decolonization measures., Results: Eleven CF patients, (median age: 9 years (range 1-43); median FEV1: 91%pred (95%CI 74%-100%pred)) who were chronically infected with MRSA, were treated daily for six months with rifampicin and fusidic acid orally. This study did not include a patient control group. Two patients had to switch to an alternative schedule, using rifampicin and clindamycin, due to the resistance pattern of MRSA. Topical decolonization measures were applied to all patients and included mupirocin-containing nasal ointment in both nostrils three times daily for five days and chlorhexidine hair and body wash once daily for five days. Microbiological eradication was achieved in all patients at the end of the six-month eradication protocol, even when significant time (range 18 months to 9 years) had elapsed since initial isolation. In only one patient MRSA reappeared in the six-month follow-up period after the initial study period. Side-effects, like nausea, vomiting and diarrhoea were seen in five out of eleven patients, but did not lead to therapy cessation., Conclusion: Chronic MRSA infection can be eradicated from respiratory tract samples using a six month dual antibiotic regimen and topical MRSA decolonization measures., (Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

We investigated the extent of convective ventilation heterogeneity contributing to the observed lung clearance index values in adult cystic fibrosis patients, as the result of two simulated scenarios, either 1) a fixed part of the lungs becoming increasingly less compliant, or 2) an increasingly greater part of the lung being less compliant. In 25 cystic fibrosis patients and 25 matched controls, we computed the lung clearance index and also quantified curvilinearity of the washout concentration curve, where curvilinearity is equal to 0 (linear in semilog plot) reflects homogeneous ventilation and curvilinearity equal to 1 corresponds to the presence of an infinitesimally slowly emptying lung unit. In the cystic fibrosis group (forced expiratory volume in 1 s 27-100% predicted), lung clearance index and curvilinearity average±sd values were 10.3±2.3 and 0.57±0.13, respectively, and were significantly different from control values (6.2±0.4 and 0.18±0.07; both p<0.001); lung clearance index and curvilinearity were also correlated (R = 0.67; p<0.001). The average curvilinearity value in the cystic fibrosis group was found to be compatible with a cumulative volume of underventilated lung of 40-50%, depending on the simulation scenario considered. The degree of washout curvilinearity observed here indicates that a major determinant of the abnormal lung clearance index values observed in adult cystic fibrosis patients is ventilation heterogeneity generated between convection-dependent lung units, while the remainder of lung clearance index abnormality with respect to normal controls potentially represents the small airways within these lung zones.

This is a case of a primary acquired pulmonary alveolar proteinosis (PAP) in an asymptomatic patient, on the waiting list for kidney transplantation, confirmed on lung biopsy and by identifying anti-GM-CSF antibodies.