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Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder which requires a complex diagnostic workup. Thus, an easy and widely available screening method would be helpful to identify patients who need a further diagnostic workup for PCD. Objectives: The aim of the study was to develop and validate a computed tomography (CT) score for PCD to facilitate etiological diagnosis in adults with bronchiectasis. Method: Chest CTs from 121 adults with bronchiectasis were scored for bronchiectasis morphology, distribution, and associated findings. Patients with and without the etiological diagnosis of PCD (46 and 75, respectively) were compared. Significantly, different imaging findings (p < 0.05) in univariate analysis were considered for multivariate analysis. Distinct findings were used to build the score. Based on this score, receiver operating characteristic (ROC) curve analysis was performed. The score was validated with 2 independent cohorts, another cohort from the same institution with 56 patients (28 with PCD) and an external cohort from another referral center with 172 patients (86 with PCD). Results: The following parameters predicted PCD in adults with bronchiectasis and were included in the score with weighting according to their regression coefficients: 2 points were given for predominance in the middle/lower lobe, 2 points for tree-in-bud pattern, 2 points for atelectasis or prior resection of a middle/lower lobe, and 3 points for absence of emphysema and fibrosis. Situs inversus was only observed in subjects with PCD (Kartagener syndrome) and, thus, was not used in the primary ciliary dyskinesia computed tomography (PCD-CT) score as group comparisons could not be performed. ROC curve analysis revealed an area under the curve (AUC) of 0.90 (95% CI 0.85–0.96). Youden index was the highest at a threshold of >6 with a sensitivity of 83% and a specificity of 83%. In the validation cohorts, ROC curve analysis confirmed the performance of the score with an AUC of 0.83 (95% CI 0.72–0.94) in the first validation cohort and 0.79 (95% CI 0.73–0.86) in the external validation cohort. Conclusions: The PCD-CT score provides the first validated CT score for PCD and helps physicians in identifying adult bronchiectasis patients who require further diagnostic workup. Key message: The PCD-CT score provides the first validated CT score to assist physicians in identifying adult bronchiectasis patients who require a further diagnostic workup for PCD. It potentially improves earlier recognition of this rare and underdiagnosed disease.

Background Lung transplantation (LTx) is a well-established treatment for end-stage pulmonary disease. However, data regarding microbiology and outcome of patients with non-cystic fibrosis bronchiectasis (NCFB) after lung transplantation are limited. Methods A retrospective analysis between August 1992 and September 2014 of all patients undergoing lung transplantation at our program of all recipients with a primary diagnosis of bronchiectasis was performed. Microbiology of sputum and bronchoalveolar lavage specimens, lung function and clinical parameters pre- and post-LTx were assessed retrospectively. Overall survival was compared to the total cohort of lung transplant recipients at institution. The survival and development of chronic lung allograft dysfunction (CLAD) was compared in patients with and without chronic Pseudomonas aeruginosa (PSA) infection after LTx. Results 34 patients were transplanted. Median age at transplantation was 40 (IQR 33–52) years. The most common etiologies of bronchiectasis were idiopathic (41%), chronic obstructive pulmonary disease (COPD) (21%) and post-infectious (15%). The most common organism of pre- and posttransplant chronic airway infection was PSA. One-year Kaplan-Meier survival for patients with bronchiectasis was 85% and 5-year survival was 73% and similar to the entire cohort. All three patients with an associated diagnosis of immunodeficiency died due to infection and sepsis within the first year. Patients with persistent colonization with Pseudomonas aeruginosa after transplantation had worse long-term survival by trend and developed chronic lung allograft dysfunction more frequently. Conclusions Overall survival of patients with bronchiectasis after LTx is comparable to other underlying diseases. A reduced survival was observed in patients with the underlying diagnosis of immunodeficiency.

We analyzed routine statutory health insurance claim data to determine prevalence of nontuberculous mycobacterial pulmonary disease in Germany. Documented prevalence rates of this nonnotifiable disease increased from 2.3 to 3.3 cases/100,000 population from 2009 to 2014. Prevalence showed a strong association with advanced age and chronic obstructive pulmonary disease.

Background Incidence and prevalence of patients with non-cystic fibrosis bronchiectasis (NCFB) appear to be increasing worldwide but supporting epidemiological data are scarce. This study assesses the incidence of NCFB patients in Germany in 2013 and analyzes comorbidities and basic patterns of resource use. Methods A representative sample of 3.988.648 anonymized persons covered by German public statutory health insurances was used to identify incident patients with NCFB in 2013. Results After extrapolation to the general population of the 728 patients found in the reference insurance database, we estimate that a total of 17,095 NCFB patients were newly diagnosed across the country in 2013 as having NCFB. This corresponds to an incidence of 21.23 per 100.000 inhabitants. The majority of NCFB patients (98.4%) was at least 18 years old, and 52.7% of the NCFB patients were male. Trend analysis shows a rise of NCFB incidence in Germany from 2011 through 2013. COPD (41.4%), asthma (32.8%) and gastroesophageal reflux (18.3%) were the most frequent predisposing conditions. Coronary heart disease was observed in more than one quarter of NCFB patients (28.2%). 58.4% of the NCFB outpatients received antiobstructive inhalative medication. Of the adult NCFB patients, 51.6% were prescribed antibiotics to treat NCFB by settled doctors (outpatient treatment); 51.5% of those patients were males. The peak of antibiotic treatment was observed in the 75–79 age group for males and 70–74 and 75–79 years for females. The majority of diagnosed patients (54.1%) received at least two prescriptions during 2013. Bacterial pathogens were coded for a total of 10.7% of NCFB patients, while Pseudomonas aeruginosa was only documented in 2.3%. Among those diagnosed in 2013, 8.0% of the adult NCFB patients who received antibiotic treatment had to be hospitalized. Conclusions Although hospital admissions due to exacerbation in the first year of diagnosing NCFB are not rare, outpatient burden and costs must also be considered a major part of care. Given the increasing recognition of NCFB, a better understanding of the economic burden of the disease is required, with a view towards improving patient management. For this, more detailed, prospective studies are needed.

Bronchiectasis represents the final pathway of several infectious, genetic, immunologic or allergic disorders. Accurate and prompt identification of the underlying cause is a key recommendation of several international guidelines, in order to tailor treatment appropriately. Primary ciliary dyskinesia (PCD) is a genetic cause of bronchiectasis in which failure of motile cilia leads to poor mucociliary clearance. Due to poor ciliary function in other organs, individuals can suffer from chronic rhinosinusitis, otitis media and infertility. This paper explores the current literature describing why, when and how to investigate PCD in adult patients with bronchiectasis. We describe the main PCD diagnostic tests and compare the two international PCD diagnostic guidelines. The expensive multi-test diagnostic approach requiring a high level of expertise and specialist equipment, make the multifaceted PCD diagnostic pathway complex. Therefore, the risk of late or missed diagnosis is high and has clinical and research implications. Defining the number of patients with bronchiectasis due to PCD is complex. To date, few studies outlining the aetiology of adult patients with bronchiectasis conduct screening tests for PCD, but they do differ in their diagnostic approach. Comparison of these studies reveals an estimated PCD prevalence of 1–13% in adults with bronchiectasis and describe patients as younger than their counterparts with moderate impairment of lung function and higher rates of chronic infection with Pseudomonas aeruginosa. Diagnosing PCD has clinical, socioeconomic and psychological implications, which affect patients’ life, including the possibility to have a specific and multidisciplinary team approach in a PCD referral centre, as well as a genetic and fertility counselling and special legal aspects in some countries. To date no specific treatments for PCD have been approved, standardized diagnostic protocols for PCD and recent diagnostic guidelines will be helpful to accurately define a population on which planning RCT studies to evaluate efficacy, safety and accuracy of PCD specific treatments.

The risk of transmission of infections in partnerships between 2 transplant recipients is unknown. The aim of this study was to evaluate transmission in such couples. In this single-center study, lung transplant (LTx) couples were identified among outpatients between 1988 and 2016. Infection rates per year and survival were compared to matched LTx-recipients not living in a transplant partnership. Twelve transplant couples were analyzed with cumulative 65 years of relationship. Overall infections were similar between LTx-couples and matched LTx-patients. No significant differences were noted in bacterial infections (.12 vs .27 per year), community-acquired viral (CARV) infections (.26 vs .22 per year), rejection treatments (.22 vs .12 per year), or hospitalizations (.26 vs .46 per year) in transplant couples and matched controls, respectively. There was no transmission of any microbial colonization from 1 partner to the other. Five cases of simultaneously detected CARV infections occurred (metapneumovirus [3], H1N1 [1], and respiratory syncytial virus [RSV; 1]). Three couples exhibited cytomegalovirus (CMV) reactivation in both partners at the same time with confirmed seronegativity before transplantation. In this case series of 12 lung transplant couples, the partnerships between 2 transplant recipients have no greater risk of bacterial infection and colonization transmission in comparison with recipients not living in a transplant relationship. However, transplant couples should be informed about the risk for transmission of viral infections, which could impact the development of chronic lung allograft dysfunction (CLAD).

Bronchiectasis is a chronic airway disease with often disabling symptoms, which is associated with excess mortality and a substantial economic burden for healthcare systems [1]. Although considered to be one of the most neglected diseases in respiratory medicine [2], bronchiectasis is apparently more common than previously thought [3, 4]. While trends regarding its epidemiology have been published for the UK and the US, with marked increases in prevalence rates reported [5–7], such studies are missing for most countries including Germany. However, these basic epidemiologic data are needed in order to inform healthcare authorities and policy makers regarding resource allocation and requirements planning. Thus, the objective of the present study was to provide insights into the trends of bronchiectasis prevalence in Germany. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Ringshausen reports grants, personal fees and other from Bayer HealthCare, grants, personal fees and other from Grifols Germany, grants, personal fees and other from Insmed Germany, personal fees from Astra Zeneca, personal fees and other from Chiesi, grants, personal fees and other from Novartis, grants and other from InfectoPharm, other from Vertex, other from Parion, other from Celtaxsys, other from Corbus, other from GSK, grants from Polyphor, personal fees and other from Boehringer Ingelheim, personal fees and other from Zambon, grants from Baslilea, other from Algipharma, outside the submitted work. Conflict of interest: Dr. Rademacher reports grants and personal fees from Bayer Health care, grants and personal fees from Insmed, grants and personal fees from Grifols, personal fees from MSD Sharp & Dohme, personal fees from Astra Zeneca, personal fees from Chiesi, outside the submitted work; . Conflict of interest: Dr. Pink reports grants from PROGNOSIS, during the conduct of the study; grants from Infectopharm, from Bayer , from Insmed, from Grifols, during the conduct of the study; personal fees and non-financial support from Berlin Chemie, personal fees and non-financial support from Boehringer Ingelheim, personal fees and non-financial support from Chiesi , outside the submitted work. Conflict of interest: Dr. de Roux has nothing to disclose. Conflict of interest: Lennart Hickstein has nothing to disclose. Conflict of interest: Tina Ploner has nothing to disclose. Conflict of interest: Dr. Welte reports grants from Grifols, Insmed, Novartis, personal fees from Grifols, Insmed, Novartis, outside the submitted work. Conflict of interest: Dr. Diel reports grants and personal fees from Bayer Vital, personal fees from Insmed Inc., outside the submitted work.

Chronic lung allograft dysfunction (CLAD) remains the leading cause of mortality in lung transplant recipients after the first year. Treatment remains limited and unpredictable. Existing data suggests extracorporeal photopheresis (ECP) may be beneficial. This study aimed to identify factors predicting treatment response and the prognostic implications. A single center retrospective analysis of all patients commencing ECP for CLAD between November 1, 2007 and September 1, 2011 was performed. In total 65 patients were included, 64 of whom had deteriorated under azithromycin. Median follow-up after commencing ECP was 503 days. Upon commencing ECP, all patients were classified using proposed criteria for emerging clinical phenotypes, including "restrictive allograft syndrome (RAS)", "neutrophilic CLAD (nCLAD)" and "rapid decliners". At follow-up, 8 patients demonstrated ≥10% improvement in FEV1 , 27 patients had stabilized and 30 patients exhibited ≥10% decline in FEV1 . Patients fulfilling criteria for "rapid decliners" (n=21, p=0.005), RAS (n=22, p=0.002) and those not exhibiting neutrophilia in bronchoalveolar lavage (n=44, p=0.01) exhibited poorer outcomes. ECP appears an effective second line treatment in CLAD patients progressing under azithromycin. ECP responders demonstrated improved progression-free survival (median 401 vs. 133 days). Proposed CLAD phenotypes require refinement, but appear to predict the likelihood of ECP response.

BACKGROUND An obstructive pattern in pulmonary function test is common after lung transplantation (LTx) and may be caused by multiple disorders. In this study, the impact and outcome of an obstructive spirometric pattern identified in transplant recipients early posttransplantation were investigated. METHODS Analyzing all patients undergoing double LTx between September 1, 2007, and October 1, 2009, we separated patients with an obstructive (forced expiratory volume in 1 sec [FEV(1)]: vital capacity [VC]

Objectives Among patients with non-cystic fibrosis bronchiectasis, 1–18% have an underlying diagnosis of primary ciliary dyskinesia (PCD) and it is suspected that there is under-recognition of this disease. Our intention was to evaluate the specific features of PCD seen on computed tomography (CT) in the cohort of bronchiectasis in order to facilitate the diagnosis. Materials and methods One hundred and twenty-one CTs performed in patients with bronchiectasis were scored for the involvement, type, and lobar distribution of bronchiectasis, bronchial dilatation, and bronchial wall thickening. Later, associated findings such as mucus plugging, tree in bud, consolidations, ground glass opacities, interlobular thickening, intralobular lines, situs inversus, emphysema, mosaic attenuation, and atelectasis were registered. Patients with PCD (n = 46) were compared to patients with other underlying diseases (n = 75). Results In patients with PCD, the extent and severity of the bronchiectasis and bronchial wall thickness were significantly lower in the upper lung lobes (p

The disease caused by nontuberculous mycobacteria (NTM) forms a broad clinical spectrum from asymptomatic infection to fatal disseminated disease in humans. While many NTM patients have underlying pulmonary diseases, NTM symptoms are undifferentiated from symptoms of patients with chronic pulmonary structural diseases [1]. Not all CF patients with MAC detected in respiratory samples require anti-mycobacterial treatment

ENaC polymorphism p.W493R is associated with bronchiectasis but does not necessarily lead to aberrant ion conductance http://ow.ly/S5Mwj

Background Accurate immunosuppression is of critical importance in preventing rejection, while avoiding toxicity following lung transplantation. The mainstay immunosuppressants are calcineurin inhibitors, which require regular monitoring due to interactions with other medications and diet. Adherence to immunosuppression and patient knowledge is vital and can be improved through patient education. Education using tablet-computers was investigated. Objective To compare tablet-PC education and conventional education in improving immunosuppression trough levels in target range 6 months after a single education. Secondary parameters were ratio of immunosuppression level measurements divided by per protocol recommended measurements, time and patient satisfaction regarding education. Design Single-centre, open labelled randomised controlled trial. Participants Patients >6 months after lung-transplantation with

Background Representative population-based data on the epidemiology of pulmonary non-tuberculous mycobacterial (PNTM) infections in Europe are limited. However, these data are needed in order to optimise patient care and to facilitate the allocation of healthcare resources. The aim of the present study was to investigate the current burden and the trends of PNTM infection-associated hospitalisations in Germany. Methods International Classification of Diseases, 10th revision (ICD-10) discharge diagnosis codes were extracted from the official nationwide diagnosis-related groups (DRG) hospital statistics in order to identify PNTM infection-associated hospitalisations (ICD-10 code A31.0) between 2005 and 2011. Poisson log-linear regression analysis was used to assess the significance of trends. Results Overall, 5,959 records with PNTM infection as any hospital discharge diagnosis were extracted from more than 125 million hospitalisations. The average annual age-adjusted rate was 0.91 hospitalisations per 100,000 population. Hospitalisation rates increased during the study period for both males and females, with the highest rate of 3.0 hospitalisations per 100,000 population among elderly men, but the most pronounced average increase of 6.4%/year among females, particularly those of young and middle age, and hospitalisations associated with cystic fibrosis. Overall, chronic obstructive pulmonary disease (COPD) was the most frequent PNTM infection-associated condition in 28.9% of hospitalisations and also showed a significant average annual increase of 4.8%. Conclusions The prevalence of PNTM infection-associated hospitalisations is steadily increasing in Germany. COPD is currently the most important associated condition. Our population-based study provides evidence of a changing epidemiology of PNTM infections and highlights emerging clinical implications.

BACKGROUND Advanced chronic lung allograft dysfunction limits survival after lung transplantation. We hypothesize that patients with chronic lung allograft dysfunction can be subdivided by exercise tolerance in two groups, and quality of life (QOL) and survival differ between the groups. METHODS A single-center, cross-sectional, partly prospective, study was performed in our outpatient clinic between July and November 2011, including all patients with a forced expiratory volume in 1 s

Lytic bone destruction is a hallmark of multiple myeloma (MM) and is because of an uncoupling of bone remodeling. Secretion of Dickkopf (DKK)-1 by myeloma cells is a major factor which causes inhibition of osteoblast precursors. In this study, the effect of different treatment regimens for MM on serum DKK-1 was evaluated and correlated with the response to treatment in 101 myeloma patients receiving bortezomib, thalidomide, lenalidomide, adriamycin and dexamethasone (AD) or high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT). At baseline, myeloma patients had increased serum DKK-1 as compared with patients with MGUS (mean 3786 pg/mL vs. 1993 pg/mL). There was no difference between previously untreated MM patients and patients at relapse. A significant decrease of DKK-1 after therapy was seen in the following groups: Bortezomib (4059 pg/mL vs. 1862 pg/mL, P = 0.016), lenalidomide (11837 pg/mL vs. 4374 pg/mL, P = 0.039), AD (1668 pg/mL vs. 1241 pg/mL, P = 0.016), and AD + HDCT + ASCT (2446 pg/mL vs. 1082 pg/mL, P = 0.001). Thalidomide led to a non-significant decrease in DKK-1 (1705 pg/mL vs. 1269 pg/mL, P = 0.081). Within all groups, a significant decrease of DKK-1 was only seen in responders (i.e. patients achieving complete remission or partial remission), but not in non-responders. We show for the first time that serum DKK-1 levels decrease in myeloma patients responding to treatment, irrespective of the regimen chosen. These data suggest that myeloma cells are the main source of circulating DKK-1 protein and provide a framework for clinical trials on anti-DKK-1 treatment in MM.

Several prognostic markers, including parameters of tumor burden and cytogenetics, were adopted to identify high-risk patients in multiple myeloma (MM). Recently, the International Staging System (ISS), including beta2-microglobulin (beta2M) and albumin, was introduced for patients with symptomatic MM. As bone disease is a hallmark of MM, we investigated the prognostic impact of the bone resorption marker carboxy-terminal telopeptide of type-1 collagen (ICTP) in combination with ISS, beta2M, albumin, deletion of chromosome 13 and high-dose therapy (HDT) in 100 patients with newly diagnosed symptomatic MM. beta2M alone, albumin alone, ISS, HDT, del(13q14) and ICTP were significant prognostic factors for overall survival (OS). In a multivariate analysis, ICTP was the most powerful prognostic factor (log-rank P0.001, hazard ratio: ninefold increase). ICTP clearly separated two subgroups with a good and a worse prognosis within each of the three ISS stages (ISS I: P=0.027, ISS II: P=0.022, ISS III: P=0.013). Incorporation of ICTP in a combined ICTP-ISS score significantly (P0.001) separated four risk groups with a 5-year OS rate of 95, 64, 46 and 22%, [corrected] respectively. These data demonstrate for the first time that the inclusion of the collagen-I degradation product ICTP, as a biomarker of bone resorption, adds to the prognostic value of ISS.

Lytic bone disease is a hallmark of multiple myeloma (MM) and is caused by osteoclast activation and osteoblast inhibition. Secretion of Dickkopf (DKK)-1 by myeloma cells is a major factor which causes inhibition of osteoblast precursors. So far, there is no study showing a significant difference in serum DKK-1 levels in MM patients with or without lytic bone lesions.DKK-1 serum levels were quantified in 184 untreated MM patients and 33 monoclonal gammopathy of undetermined significance (MGUS) patients by ELISA, using a monoclonal anti-DKK-1 antibody.Serum DKK-1 was elevated in MM as compared with MGUS (mean 11 963 pg/mL vs. 1993 pg/mL; P0.05). Serum DKK-1 levels significantly correlated with myeloma stage according to Durie and Salmon (mean 2223 pg/mL vs. 15 209 pg/mL in stage I and II/III, respectively; P = 0.005). Importantly, myeloma patients without lytic lesions in conventional radiography had significantly lower DKK-1 levels than patients with lytic bone disease (mean 3114 pg/mL vs. 17 915 pg/mL; P = 0.003). Of interest, serum DKK-1 correlated with the number of bone lesions (0 vs. 1-3 vs.3 lesions: 3114 pg/mL vs. 3559 pg/mL vs. 24 068 pg/mL; P = 0.002).Using a large series of myeloma patients, we could show for the first time a correlation between DKK-1 serum concentration and the amount of lytic bone disease, indicating that DKK-1 is an important factor for the extent of bone disease and supporting the hypothesis of DKK-1 as a therapeutic target in myeloma bone disease.