Bronchiectasis and asthma: Data from the European Bronchiectasis Registry (EMBARC).

BACKGROUND: Asthma is commonly reported in patients with a diagnosis of bronchiectasis. OBJECTIVE: The aim of this study was to evaluate whether patients with bronchiectasis and asthma (BE+A) had a different clinical phenotype and different outcomes compared with patients with bronchiectasis without concomitant asthma. METHODS: A prospective observational pan-European registry (European Multicentre Bronchiectasis Audit and Research Collaboration) enrolled patients across 28 countries. Adult patients with computed tomography-confirmed bronchiectasis were reviewed at baseline and annual follow-up visits using an electronic case report form. Asthma was diagnosed by the local investigator. Follow-up data were used to explore differences in exacerbation frequency between groups using a negative binomial regression model. Survival analysis used Cox proportional hazards regression. RESULTS: Of 16,963 patients with bronchiectasis included for analysis, 5,267 (31.0%) had investigator-reported asthma. Patients with BE+A were younger, were more likely to be female and never smokers, and had a higher body mass index than patients with bronchiectasis without asthma. BE+A was associated with a higher prevalence of rhinosinusitis and nasal polyps as well as eosinophilia and Aspergillus sensitization. BE+A had similar microbiology but significantly lower severity of disease using the bronchiectasis severity index. Patients with BE+A were at increased risk of exacerbation after adjustment for disease severity and multiple confounders. Inhaled corticosteroid (ICS) use was associated with reduced mortality in patients with BE+A (adjusted hazard ratio 0.78, 95% CI 0.63-0.95) and reduced risk of hospitalization (rate ratio 0.67, 95% CI 0.67-0.86) compared with control subjects without asthma and not receiving ICSs. CONCLUSIONS: BE+A was common and was associated with an increased risk of exacerbations and improved outcomes with ICS use. Unexpectedly we identified significantly lower mortality in patients with BE+A.

Airway clearance management in people with bronchiectasis: data from the European Bronchiectasis Registry (EMBARC).

BACKGROUND: International guidelines recommend airway clearance management as one of the important pillars of bronchiectasis treatment. However, the extent to which airway clearance is used for people with bronchiectasis in Europe is unclear. The aim of the study was to identify the use of airway clearance management in patients with bronchiectasis across different countries and factors influencing airway clearance use. METHODS: This was a prospective observational study using data from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) Registry between January 2015 and April 2022. Prespecified options for airway clearance management were recorded, including airway clearance techniques, devices and use of mucoactive drugs. RESULTS: 16 723 people with bronchiectasis from 28 countries were included in the study. The mean age was 67 years (interquartile range 57-74 years, range 18-100 years) and 61% were female. 72% of the participants reported daily sputum expectoration and 52% (95% CI 51-53%) of all participants reported using regular airway clearance management. Active cycle of breathing technique was used by 28% of the participants and airway clearance devices by 16% of participants. The frequency of airway clearance management and techniques used varied significantly between different countries. Participants who used airway clearance management had greater disease severity and worse symptoms, including a higher daily sputum volume, compared to those who did not use it regularly. Mucoactive drugs were also more likely to be used in participants with more severe disease. Access to specialist respiratory physiotherapy was low throughout Europe, but particularly low in Eastern Europe. CONCLUSIONS: Only a half of people with bronchiectasis in Europe use airway clearance management. Use of and access to devices, mucoactive drugs and specialist chest physiotherapy appears to be limited in many European countries.

Objective sputum colour assessment and clinical outcomes in bronchiectasis: data from the European Bronchiectasis Registry (EMBARC).

BACKGROUND: A validated 4-point sputum colour chart can be used to objectively evaluate the levels of airway inflammation in bronchiectasis patients. In the European Bronchiectasis Registry (EMBARC), we tested whether sputum colour would be associated with disease severity and clinical outcomes. METHODS: We used a prospective, observational registry of adults with bronchiectasis conducted in 31 countries. Patients who did not produce spontaneous sputum were excluded from the analysis. The Murray sputum colour chart was used at baseline and at follow-up visits. Key outcomes were frequency of exacerbations, hospitalisations for severe exacerbations and mortality during up to 5-year follow-up. RESULTS: 13 484 patients were included in the analysis. More purulent sputum was associated with lower forced expiratory volume in 1 s (FEV1), worse quality of life, greater bacterial infection and a higher bronchiectasis severity index. Sputum colour was strongly associated with the risk of future exacerbations during follow-up. Compared to patients with mucoid sputum (reference group), patients with mucopurulent sputum experienced significantly more exacerbations (incident rate ratio (IRR) 1.29, 95% CI 1.22-1.38; p<0.0001), while the rates were even higher for patients with purulent (IRR 1.55, 95% CI 1.44-1.67; p<0.0001) and severely purulent sputum (IRR 1.91, 95% CI 1.52-2.39; p<0.0001). Hospitalisations for severe exacerbations were also associated with increasing sputum colour with rate ratios, compared to patients with mucoid sputum, of 1.41 (95% CI 1.29-1.56; p<0.0001), 1.98 (95% CI 1.77-2.21; p<0.0001) and 3.05 (95% CI 2.25-4.14; p<0.0001) for mucopurulent, purulent and severely purulent sputum, respectively. Mortality was significantly increased with increasing sputum purulence, hazard ratio 1.12 (95% CI 1.01-1.24; p=0.027), for each increment in sputum purulence. CONCLUSION: Sputum colour is a simple marker of disease severity and future risk of exacerbations, severe exacerbations and mortality in patients with bronchiectasis.

Versatile and Easily Designable Polyester-Laser Toner Interfaces for Site-Oriented Adsorption of Antibodies.

Laser toners appear as attractive materials for barriers and easily laminated interphases for Lab-on-a-Foil microfluidics, due to the excellent adhesion to paper and various membranes or foils. This work shows for the first time a comprehensive study on the adsorption of antibodies on toner-covered poly(ethylene terephthalate) (PET@toner) substrates, together with assessment of such platforms in rapid prototyping of disposable microdevices and microarrays for immunodiagnostics. In the framework of presented research, the surface properties and antibody binding capacity of PET substrates with varying levels of toner coverage (0-100%) were characterized in detail. It was proven that polystyrene-acrylate copolymer-based toner offers higher antibody adsorption efficiency compared with unmodified polystyrene and PET as well as faster adsorption kinetics. Comparative studies of the influence of pH on the effectiveness of antibodies immobilization as well as measurements of surface ζ-potential of PET, toner, and polystyrene confirmed the dominant role of hydrophobic interactions in adsorption mechanism. The applicability of PET@toner substrates as removable masks for protection of foil against permanent hydrophilization was also shown. It opens up the possibility of precise tuning of wettability and antibody binding capacity. Therefore, PET@toner foils are presented as useful platforms in the construction of immunoarrays or components of microfluidic systems.

Blood eosinophil count and airway epithelial transcriptome relationships in COPD versus asthma.

BACKGROUND: Whether the clinical or pathophysiologic significance of the "treatable trait" high blood eosinophil count in COPD is the same as for asthma remains controversial. We sought to determine the relationship between the blood eosinophil count, clinical characteristics and gene expression from bronchial brushings in COPD and asthma. METHODS: Subjects were recruited into a COPD (emphysema versus airway disease [EvA]) or asthma cohort (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes, U-BIOPRED). We determined gene expression using RNAseq in EvA (n = 283) and Affymetrix microarrays in U-BIOPRED (n = 85). We ran linear regression analysis of the bronchial brushings transcriptional signal versus blood eosinophil counts as well as differential expression using a blood eosinophil > 200 cells/µL as a cut-off. The false discovery rate was controlled at 1% (with continuous values) and 5% (with dichotomized values). RESULTS: There were no differences in age, gender, lung function, exercise capacity and quantitative computed tomography between eosinophilic versus noneosinophilic COPD cases. Total serum IgE was increased in eosinophilic asthma and COPD. In EvA, there were 12 genes with a statistically significant positive association with the linear blood eosinophil count, whereas in U-BIOPRED, 1197 genes showed significant associations (266 positive and 931 negative). The transcriptome showed little overlap between genes and pathways associated with blood eosinophil counts in asthma versus COPD. Only CST1 was common to eosinophilic asthma and COPD and was replicated in independent cohorts. CONCLUSION: Despite shared "treatable traits" between asthma and COPD, the molecular mechanisms underlying these clinical entities are predominately different.

Emphysema- and airway-dominant COPD phenotypes defined by standardised quantitative computed tomography.

EvA (Emphysema versus Airway disease) is a multicentre project to study mechanisms and identify biomarkers of emphysema and airway disease in chronic obstructive pulmonary disease (COPD). The objective of this study was to delineate objectively imaging-based emphysema-dominant and airway disease-dominant phenotypes using quantitative computed tomography (QCT) indices, standardised with a novel phantom-based approach.441 subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-3) were assessed in terms of clinical and physiological measurements, laboratory testing and standardised QCT indices of emphysema and airway wall geometry.QCT indices were influenced by scanner non-conformity, but standardisation significantly reduced variability (p<0.001) and led to more robust phenotypes. Four imaging-derived phenotypes were identified, reflecting "emphysema-dominant", "airway disease-dominant", "mixed" disease and "mild" disease. The emphysema-dominant group had significantly higher lung volumes, lower gas transfer coefficient, lower oxygen (PO2 ) and carbon dioxide (PCO2 ) tensions, higher haemoglobin and higher blood leukocyte numbers than the airway disease-dominant group.The utility of QCT for phenotyping in the setting of an international multicentre study is improved by standardisation. QCT indices of emphysema and airway disease can delineate within a population of patients with COPD, phenotypic groups that have typical clinical features known to be associated with emphysema-dominant and airway-dominant disease.

Pilot program on distance training in spirometry testing - the technology feasibility study.

INTRODUCTION: Office spirometry has been widely used in recent years by general practitioners in primary care setting, thus the need for stricter monitoring of the quality of spirometry has been recognized. MATERIAL AND METHODS: A spirometry counseling network of outpatients clinics was created in Poland using portable spirometer Spirotel. The spirometry data were transferred to counseling centre once a week. The tests sent to the counseling centre were analyzed by doctors experienced in the analysis of spirometric data. In justified cases they sent their remarks concerning performed tests to the centres via e-mail. RESULTS: We received 878 records of spirometry tests in total. Data transmission via the telephone was 100% effective. The quality of spirometry tests performed by outpatients clinics was variable. CONCLUSIONS: The use of spirometers with data transfer for training purposes seems to be advisable. There is a need to proper face-to-face training of spirometry operators before an implementation of any telemedicine technology.

Methotrexate as a single agent for treating pulmonary sarcoidosis: a single centre real-life prospective study.

INTRODUCTION: The first-line therapy in chronic sarcoidosis, according to WASOG/ATS/ERS recommendations, is GCS. This therapy is associated with significant adverse effects and finally does not alter the natural history of the disease. The objective of our study was to evaluate the efficacy and safety of monotherapy with MTX, as an alternative to GCS, in progressive pulmonary sarcoidosis. MATERIAL AND METHODS: An open prospective real-life, single-centre trial was performed on 50 patients with biopsy proven sarcoidosis, 28M and 22F, mean age 45.55 ± 8.9 years. The average duration of disease before MTX therapy was 12.34 ± 20.49 years, GCS therapy in the past was applied in 41 patients. All patients received MTX (10 mg or 15 mg weekly) between 2004 and 2013 because of chronic progressive pulmonary sarcoidosis. Therapy was planned for 24 months. Patients underwent regular clinical evaluation, pulmonary function assessment, exercise ability testing (6MWT), and chest radiography for therapy effectiveness every six months and side effects monitoring every 4-6 weeks. Forty-nine patients were included for statistical analysis of treatment efficacy. They were retrospectively allocated to "MTX responder" group if an improvement of 10% of FEV1, FVC, TLC, or 15% of DLCO from the initial value was documented for at least one parameter or "non-responders" if the patient did not meet the above-mentioned criteria. RESULTS: Duration of treatment ranged from 6 to 24 months, mean time 60.75 ± 34.1 weeks. For the whole cohort significant improvement after MTX therapy was observed for minimal SaO2 (%) (p = 0.043) and for decrease of DSaO2 (%) (p = 0.048) in six-minute walk test. The results were significantly better for patients treated with 15 mg than for those treated with 10 mg weekly and for those who obtained a greater total amount of MTX during therapy. Significant difference of DLCO%pred was observed after six months of MTX therapy between groups treated 15 mg vs 10 mg weekly (73.27 ± 12.7% vs. 63.15 ± 16.4%, p = 0.03). Twenty-five patients (55%) met the criteria of "MTX responders" group. Patients who responded well to treatment had significantly lower TLC and FVC initial values comparing to "MTX non-responders". After treatment the only significant difference in PFT between groups was noted for DLCO%pred. Eleven patients (22%) stopped the treatment due to adverse events of MTX, mild hepatic abnormalities were observed in ten patients (20%), and concomitant infection was found in four patients. There were no patients with a fatal outcome. CONCLUSIONS: MTX as a single agent in the treatment of sarcoidosis has proved to be a safe and effective steroid alternative. Selected patients with chronic pulmonary sarcoidosis experience definite PFT improvements after MTX treatment. There is need to search for predictors of MTX treatment effectiveness.

Impact of mild anaemia on dyspnoea during exertion and exercise tolerance in patients with acute exacerbation of chronic obstructive pulmonary disease.

INTRODUCTION: Dyspnoea and decreased exercise tolerance are symptoms of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Anaemia is a risk factor for reduced functional capacity and dyspnoea in stable COPD. There is limited information about the impact of anaemia on functional capacity and dyspnoea of patients during AECOPD. The aim of this study was to evaluate the impact of decreased blood haemoglobin concentration on the results of six-minute walking test (6MWT) in patients during AECOPD. MATERIAL AND METHODS: A post hoc analysis of data collected from prospective long-term studies on AECOPD. Haemoglobin concentration from the first obtainable hospital measurement were included in the assessment. 6MWT was performed after clinical improvement of the patient. Dyspnoea at baseline and after exercise and oxygen saturation (SpO(2)) during exercise was measured. RESULTS: (presented as means ± SD): 402 patients with exacerbation of COPD (COPD stage 3.5 ± 0.6) were examined. Patients with anaemia (26% of those studied, age 74.5 ± 8.2 years) achieved 258.1 ± 125.1 m during 6MWT, with exertional desaturation of 2.9 ± 2.6%. Patients without anaemia (74% of those studied, age 70.2 ± 8.7 years) achieved 271 ± 136.0 m during 6MWT with exertional desaturation of 3.8 ± 3.7%. The haemoglobin concentration did not correlate with 6MWT, dyspnoea during 6MWT, or exercise oxygenation and blood desaturation during exercise. CONCLUSION: Mildly decreased blood haemoglobin concentration did not influence the results of 6MWT in patients with AECOPD.

Fatal clinical outcome in a patient with sarcoidosis-lymphoma syndrome.

A 62-year-old female suspected of malignant disease underwent a splenectomy that revealed noncaseating granulomas in the histological specimen. Chest X-ray (CXR) and lung CT scans suggested sarcoidosis stage II. TBLB showed noncaseating granulomas. A diagnosis of sarcoidosis was made. Initially no treatment was needed as partial remission on CXR and normal lung function were observed. During the follow up she underwent open lung biopsy and axillary lymph node biopsy because of radiological progression with presence of CXR opacities imitating metastases and recurrent lymphadenopathy. No malignant cells were found. Spontaneous partial resolution of disseminated changes on the CXR was observed. Because of progressive deterioration in lung function and the clinical course of the disease strongly suggesting the progression of systemic sarcoidosis, the patient was given steroid treatment, which initially resulted in partial remission of pulmonary disseminated changes, peripheral lymphadenopathy and improvement in lung function test. Eight months later severe deterioration in general condition, anaemia, leukocytosis, hypoxemia, massive hepatomegaly and recurrence of general lymphadenopathy along with progression of disseminated changes were found. She died before the final diagnosis was established. Post-mortem examination showed a nodal marginal zone B-cell lymphoma with monocytoid B-cells, according to WHO classification. The malignant cells were found in the jugular, mediastinal, paratracheal, paragastric, paraintestinal and retroperitoneal lymph nodes and they infiltrated the lungs, pleura, liver, thyroid gland and pancreas. No sarcoid granulomas were found in the autopsy.

The impact of comorbidities on tuberculosis treatment outcomes in Poland: a national cohort study.

Background: Tuberculosis (TB) is a complex disease associated with other medical conditions, that may affect disease severity. This study aimed to investigate the impact of comorbidities on treatment outcomes and mortality rates in patients with TB in Poland. Methods: We analyzed a national cohort of 19,217 adult TB patients diagnosed between 2011 and 2016 in Poland. We compared treatment success rates and mortality rates in patients with comorbidities and those without to assess the impact of various comorbidities on these outcomes. Odds ratios (OR) were calculated to quantify the association between comorbidities and TB treatment outcomes. Results: Patients with comorbidities had lower treatment success rates and higher mortality rates. Diabetes was identified as a significant risk factor for increased TB mortality (OR = 1.9) and mortality from all other causes (OR = 4.5). Similar associations were found for alcoholism (OR = 8.3 and OR = 7.1), immunosuppressive therapy (OR = 5.7 and OR = 5.9), and cancer (OR = 3.4 and OR = 15.4). HIV and tobacco use were associated with an increased risk of mortality from causes other than TB, with odds ratios of 28.6 and 2.2, respectively. The overall treatment success rate in the study population was 88.0%, with 9.2% of patients failing to achieve treatment success and 2.8% dying. Comorbidities such as diabetes, alcoholism, substance addiction, immunosuppressive therapy, cancer, and tobacco use increased the risk of tuberculosis treatment failure. Conclusion: Patients with comorbidities face a higher risk of unsuccessful treatment outcomes and increased mortality. It is essential to implement integrated management strategies that address both TB and comorbid conditions to improve treatment success rates and reduce mortality.

The EvA study: aims and strategy.

The EvA study is a European Union-funded project under the Seventh Framework Programme (FP7), which aims at defining new markers for chronic obstructive pulmonary disease (COPD) and its subtypes. The acronym is derived from emphysema versus airway disease, indicating that the project targets these two main phenotypes of the disease. The EvA study is based on the concept that emphysema and airway disease are governed by different pathophysiological processes, are driven by different genes and have differential gene expression in the lung. To define these genes, patients and non-COPD controls are recruited for clinical examination, lung function analysis and computed tomography (CT) of the lung. CT scans are used to define the phenotypes based on lung density and airway wall thickness. This is followed by bronchoscopy in order to obtain samples from the airways and the alveoli. These tissue samples, along with blood samples, are then subjected to genome-wide expression and association analysis and markers linked to the phenotypes are identified. The population of the EvA study is different from other COPD study populations, since patients with current oral glucocorticoids, antibiotics and exacerbations or current smokers are excluded, such that the signals detected in the molecular analysis are due to the distinct inflammatory process of emphysema and airway disease in COPD.

[Autoimmunological pulmonary alveolar proteinosis--case report]. / Autoimmunologiczna proteinoza pecherzyków plucnych--opis przypadku.

Autoimmunological pulmonary alveolar proteinosis (APAP) is a rare interstitial lung disease with abnormal surfactant homeostasis. Autoimmunological pulmonary alveolar proteinosis is diagnosed most often in the third or fourth decade of life. Predominant symptoms are dyspnea and cough. In most cases, disease is mild but in more severe cases when dyspnea limits patient physical activity a treatment is required. The most common treatment procedure is a whole-lung lavage. We present a case study of 37 years old woman with the patchy consolidations in the chest radiograph. High resolution computed tomography (HRCT) image suggested hipersensivity pneumonitis. At the beginning due to limited disease symptoms no specific proceedings was implemented. After two year follow-up of non-resolving pulmonary changes the decision about open lung biopsy was made. On the basis of histological examination of samples and presence of anty GM-CSF antibodies the diagnosis of autoimmunological pulmonary alveolar proteinosis was established.

Detection of SARS-CoV-2 Using Reverse Transcription Helicase Dependent Amplification and Reverse Transcription Loop-Mediated Amplification Combined with Lateral Flow Assay.

Rapid and accurate detection and identification of pathogens in clinical samples is essential for all infection diseases. However, in the case of epidemics, it plays a key role not only in the implementation of effective therapy but also in limiting the spread of the epidemic. In this study, we present the application of two nucleic acid isothermal amplification methods-reverse transcription helicase dependent amplification (RT-HDA) and reverse transcription loop-mediated amplification (RT-LAMP)-combined with lateral flow assay as the tools for the rapid detection of SARS-CoV-2, the etiological agent of COVID-19, which caused the ongoing global pandemic. In order to optimize the RT-had, the LOD was 3 genome copies per reaction for amplification conducted for 10-20 min, whereas for RT-LAMP, the LOD was 30-300 genome copies per reaction for a reaction conducted for 40 min. No false-positive results were detected for RT-HDA conducted for 10 to 90 min, but false-positive results occurred when RT-LAMP was conducted for longer than 40 min. We concluded that RT-HDA combined with LFA is more sensitive than RT-LAMP, and it is a good alternative for the development of point-of-care tests for SARS-CoV-2 detection as this method is simple, inexpensive, practical, and does not require qualified personnel to perform the test and interpret its results.

[The impact of comorbidities on the length of hospital treatment in patients with chronic obstructive pulmonary disease]. / Wplyw chorób wspólistniejacych na dlugosc leczenia szpitalnegou chorych z zaostrzeniem przewleklej obturacyjnej choroby pluc.

INTRODUCTION: The aim of this study was to assess relationships of chronic obstructive pulmonary disease (COPD) comorbidities number, with the duration of hospital stay due to acute AE COPD in longitudinal prospective study. MATERIAL AND METHODS: We evaluated the number of re-hospitalizations, length of stay and number of comorbidities in 464 consecutive COPD patients admitted to the tertiary respiratory hospital due to AE COPD enrolled in longitudinal prospective study from 2005 to 2009 year. RESULTS: GOLD II stage COPD patients had 4.1 ± 1.2 comorbidities (p = 0.002), stage III 3.4 ± 1.3 and stage IV had 3.6 ± 1.2 comorbidities. Duration of hospital stay (medians) was longer in more severe patients. Duration of hospitalization correlated with urea level (r = 0.19 p 〈 0.001), pCO(2) (r = 0.193, p = 0.0003), HCO(3) (r = 0.25, p 〈 0.0001), haemoglobin (r = -0.18, p 〈 0.001), and hematocrit (r = -0.13, p = 0.008). The patients with the risk of readmission had more severe GOLD stage and were hypercapnic (pCO(2) = 47.6 mmHg v. 43.9 mmHg in those without hospitalization). CONCLUSIONS: The haemoglobin level, hypercapnia and renal function are predictors of prolonged hospitalization. Patients with more severe airflow limitation and higher pCO(2) have increased risk for readmission to the hospital. More severe disease stage, clinical diagnosis of cor pulmonale or bronchiectasis was related to longer hospital stay.

The influence of comorbidities on mortality in bronchiectasis: A prospective, observational study.

BACKGROUND: Bronchiectasis is a progressive chronic disease associated with an increased risk of mortality. OBJECTIVES: To identify the prevalence of comorbidities in patients with bronchiectasis and the impact of these comorbidities on mortality. MATERIAL AND METHODS: A cohort of 93 patients with computed tomography (CT)-confirmed bronchiectasis admitted consecutively to a tertiary teaching hospital was observed over a period of 5 years. All patients were carefully observed for comorbidities and mortality. RESULTS: A total of 43 men (46.2%) and 50 women (53.8%) with a median age of 66.0 years (interquartile range (IQR) 59.7-74.0 years), and a median of 3 comorbidities at baseline (IQR 1-5) were observed. The mortality rate during the observation period was 16%. The median number of comorbidities was significantly higher in the group of non-survivors (5 (IQR 3-5.75)) compared with survivors (3 (IQR 1-4); p = 0.0100). The burden of comorbidities was associated with an increased hazard of death: having 4 or more comorbidities was associated with an increased risk of death compared to patients with 2 or 3 coexisting illnesses (hazard ratio (HR) = 1.35 (95% confidence interval (95% CI) [0.41, 4.41]); p = 0.0494). The Bronchiectasis Aetiology Comorbidity Index (BACI) was a significant predictor of death in patients with severe bronchiectasis. CONCLUSION: We found a significant number of comorbidities in patients with bronchiectasis. In these patients, the comorbidity burden has an impact on mortality. The BACI is a useful tool for the clinical assessment of patients with severe bronchiectasis.

Lung microbiome composition and bronchial epithelial gene expression in patients with COPD versus healthy individuals: a bacterial 16S rRNA gene sequencing and host transcriptomic analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with airway inflammation and bacterial dysbiosis. The relationship between the airway microbiome and bronchial gene expression in COPD is poorly understood. We aimed to identify differences in the airway microbiome from bronchial brushings in patients with COPD and healthy individuals and to investigate whether any distinguishing bacteria are related to bronchial gene expression. METHODS: For this 16S rRNA gene sequencing and host transcriptomic analysis, individuals aged 45-75 years with mild-to-moderate COPD either receiving or not receiving inhaled corticosteroids and healthy individuals in the same age group were recruited as part of the Emphysema versus Airways Disease (EvA) consortium from nine centres in the UK, Germany, Italy, Poland, and Hungary. Individuals underwent clinical characterisation, spirometry, CT scans, and bronchoscopy. From bronchoscopic bronchial brush samples, we obtained the microbial profiles using 16S rRNA gene sequencing and gene expression using the RNA-Seq technique. We analysed bacterial genera relative abundance and the associations between genus abundance and clinical characteristics or between genus abundance and host lung transcriptional signals in patients with COPD versus healthy individuals, and in patients with COPD with versus without inhaled corticosteroids treatment. FINDINGS: Between February, 2009, and March, 2012, we obtained brush samples from 574 individuals. We used 546 of 574 samples for analysis, including 207 from healthy individuals and 339 from patients with COPD (192 with inhaled corticosteroids and 147 without). The bacterial genera that most strongly distinguished patients with COPD from healthy individuals were Prevotella (median relative abundance 33·5%, IQR 14·5-49·4, in patients with COPD vs 47·7%, 31·1-60·7, in healthy individuals; p<0·0001), Streptococcus (8·6%, 3·8-15·8, vs 5·3%, 3·0-10·1; p<0·0001), and Moraxella (0·05%, 0·02-0·14, vs 0·02%, 0-0·07; p<0·0001). Prevotella abundance was inversely related to COPD severity in terms of symptoms and positively related to lung function and exercise capacity. 446 samples had assessable RNA-seq data, 257 from patients with COPD (136 with inhaled corticosteroids and 121 without) and 189 from healthy individuals. No significant associations were observed between lung transcriptional signals from bronchial brushings and abundance of bacterial genera in patients with COPD without inhaled corticosteroids treatment and in healthy individuals. In patients with COPD treated with inhaled corticosteroids, Prevotella abundance was positively associated with expression of epithelial genes involved in tight junction promotion and Moraxella abundance was associated with expression of the IL-17 and TNF inflammatory pathways. INTERPRETATION: With increasing severity of COPD, the airway microbiome is associated with decreased abundance of Prevotella and increased abundance of Moraxella in concert with downregulation of genes promoting epithelial defence and upregulation of pro-inflammatory genes associated with inhaled corticosteroids use. Our work provides further insight in understanding the relationship between microbiome alteration and host inflammatory response, which might lead to novel therapeutic strategies for COPD. FUNDING: EU Seventh Framework Programme, National Institute for Health Research.

Gender specific airway gene expression in COPD sub-phenotypes supports a role of mitochondria and of different types of leukocytes.

Chronic obstructive pulmonary disease (COPD) is a destructive inflammatory disease and the genes expressed within the lung are crucial to its pathophysiology. We have determined the RNAseq transcriptome of bronchial brush cells from 312 stringently defined ex-smoker patients. Compared to healthy controls there were for males 40 differentially expressed genes (DEGs) and 73 DEGs for females with only 26 genes shared. The gene ontology (GO) term "response to bacterium" was shared, with several different DEGs contributing in males and females. Strongly upregulated genes TCN1 and CYP1B1 were unique to males and females, respectively. For male emphysema (E)-dominant and airway disease (A)-dominant COPD (defined by computed tomography) the term "response to stress" was found for both sub-phenotypes, but this included distinct up-regulated genes for the E-sub-phenotype (neutrophil-related CSF3R, CXCL1, MNDA) and for the A-sub-phenotype (macrophage-related KLF4, F3, CD36). In E-dominant disease, a cluster of mitochondria-encoded (MT) genes forms a signature, able to identify patients with emphysema features in a confirmation cohort. The MT-CO2 gene is upregulated transcriptionally in bronchial epithelial cells with the copy number essentially unchanged. Both MT-CO2 and the neutrophil chemoattractant CXCL1 are induced by reactive oxygen in bronchial epithelial cells. Of the female DEGs unique for E- and A-dominant COPD, 88% were detected in females only. In E-dominant disease we found a pronounced expression of mast cell-associated DEGs TPSB2, TPSAB1 and CPA3. The differential genes discovered in this study point towards involvement of different types of leukocytes in the E- and A-dominant COPD sub-phenotypes in males and females.

Glomerular filtration rate in patients with obstructive sleep apnea: the influence of cystatin-C-based estimations and comorbidity.

BACKGROUND: Recent studies indicate that chronic kidney disease (CKD) is a comorbidity in patients with obstructive sleep apnea (OSA). We hypothesized that the use of the classical muscle-dependent, creatinine-based equation to estimate glomerular filtration rate (GFR) in patients with OSA may be inaccurate due to the extreme body mass index (BMI) of some patients. The aim of this study was to establish the role of cystatin-C-based estimation of GFR for the detection of CKD in patients with OSA and typical comorbidities. METHODS: Two hundred and forty consecutive patients with newly diagnosed OSA were enrolled into this cross-sectional study. In all patients estimated GFR (eGFR) was calculated with chronic kidney disease-epidemiology collaboration group (CKD-EPI) equations using creatinine and cystatin-C. All patients were examined for comorbidities. RESULTS: In obese patients with OSA significant differences between GFR estimations based on creatinine and cystatin were found: eGFR based on muscle-dependent creatinine measurement was significantly higher than the muscle-independent eGFR based on cystatin-C measurement. CONCLUSIONS: GFR can be routinely screened for using creatinine-based estimations (eGFRcreat). In a selected group of patients with OSA with BMI over 30 kg/m2 the addition of cystatin-C for assessment of eGFR is suggested.

Does bronchiectasis affect COPD comorbidities?

INTRODUCTION: COPD and bronchiectasis, chronic inflammation disorders of the bronchial tree through the mechanism of 'spill-over' of inflammatory mediators, may lead to systemic manifestations of illness of the respiratory system and comorbidities. The aim of the study was to evaluate the frequency of coexisting chronic obstructive pulmonary disease and bronchiectasis and influence of bronchiectasis on COPD comorbid diseases. MATERIAL AND METHODS: A post-hoc cross-sectional analysis of cohort study of 288 consecutive patients hospitalized due to acute exacerbation of COPD was performed. RESULTS: 177 males (61.5%) and 111 females (38.5%) with mean age = 71.0 8 ± 8.9 yrs, FEV1 % pred. = 34.6 ± 16.8 with COPD diagnosis were studied. In this group, 29 (10.1%) patients presented with bronchiectasis confirmed by HRCT scan. COPD patients with and without bronchiectasis had similar Charlson index results (2.5 vs 2.1, p=0.05). COPD patients with bronchiectasis required longer hospitalization during exacerbation. COPD patients with bronchiectasis significantly more often than patients without this comorbidity revealed the features of colonization with P. aeruginosa (OR = 4.17, p = 0.02). CONCLUSIONS: Bronchiectasis is a relatively common comorbidity in COPD patients. COPD patients with bronchiectasis are more frequently colonized with P. aruginosa comparing to non-bronchiectasis COPD patients. We did not confirm the influence of bronchiectasis on COPD comorbidities.