Non-Invasive Cardiac Output Measurement Using Inert Gas Rebreathing Method during Cardiopulmonary Exercise Testing-A Systematic Review.

BACKGROUND: The use of inert gas rebreathing for the non-invasive cardiac output measurement has produced measurements comparable to those obtained by various other methods. However, there are no guidelines for the inert gas rebreathing method during a cardiopulmonary exercise test (CPET). In addition, there is also a lack of specific standards for assessing the non-invasive measurement of cardiac output during CPET, both for healthy patients and those suffering from diseases and conditions. AIM: This systematic review aims to describe the use of IGR for a non-invasive assessment of cardiac output during cardiopulmonary exercise testing and, based on the information extracted, to identify a proposed CPET report that includes an assessment of the cardiac output using the IGR method. METHODS: This systematic review was conducted by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta Analyses) guidelines. PubMed, Web of Science, Scopus, and Cochrane Library databases were searched from inception until 29 December 2022. The primary search returned 261 articles, of which 47 studies met the inclusion criteria for this review. RESULTS AND CONCLUSIONS: This systematic review provides a comprehensive description of protocols, indications, technical details, and proposed reporting standards for a non-invasive cardiac output assessment using IGR during CPET. It highlights the need for standardized approaches to CPET and identifies gaps in the literature. The review critically analyzes the strengths and limitations of the studies included and offers recommendations for future research by proposing a combined report from CPET-IGR along with its clinical application.

Baseline characteristics from a 3-year longitudinal study to phenotype subjects with COPD: the FOOTPRINTS study.

BACKGROUND: FOOTPRINTS® is a prospective, longitudinal, 3-year study assessing the association between biomarkers of inflammation/lung tissue destruction and chronic obstructive pulmonary disease (COPD) severity and progression in ex-smokers with mild-to-severe COPD. Here, we present baseline characteristics and select biomarkers of study subjects. METHODS: The methodology of FOOTPRINTS® has been published previously. The study population included ex-smokers with a range of COPD severities (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages 1-3), ex-smokers with COPD and alpha-1-antitrypsin deficiency (A1ATD) and a control group of ex-smokers without airflow limitation (EwAL). At study entry, data were collected for: demographics, disease characteristics, history of comorbidities and COPD exacerbations, symptoms, lung function and volume, exercise capacity, soluble biomarkers, and quantitative and qualitative computed tomography. Baseline data are presented with descriptive statistical comparisons for soluble biomarkers in the individual GOLD and A1ATD groups versus EwAL. RESULTS: In total, 463 subjects were enrolled. The per-protocol set comprised 456 subjects, mostly male (64.5%). The mean (standard deviation) age was 60.7 (6.9) years. At baseline, increasing pulmonary symptoms, worse lung function, increased residual volume, reduced diffusing capacity of the lung for carbon monoxide (DLco) and greater prevalence of centrilobular emphysema were observed with increasing disease severity amongst GOLD 1-3 subjects. Subjects with A1ATD (n = 19) had similar lung function parameters to GOLD 2-3 subjects, a high residual volume comparable to GOLD 3 subjects, and similar air trapping to GOLD 2 subjects. Compared with EwAL (n = 61), subjects with A1ATD had worse lung function, increased residual volume, reduced DLco, and a greater prevalence of confluent or advanced destructive emphysema. The soluble inflammatory biomarkers white blood cell count, fibrinogen, high-sensitivity C-reactive protein and plasma surfactant protein were higher in GOLD 1-3 groups than in the EwAL group. Interleukin-6 was expressed less often in EwAL subjects compared with subjects in the GOLD and A1ATD groups. Soluble receptor for advanced glycation end product was lowest in GOLD 3 subjects, indicative of more severe emphysema. CONCLUSIONS: These findings provide context for upcoming results from FOOTPRINTS®, which aims to establish correlations between biomarkers and disease progression in a representative COPD population. TRIAL REGISTRATION NUMBER: NCT02719184, study start date 13/04/2016.

Genome-engineering technologies for modeling and treatment of cystic fibrosis.

Cystic fibrosis (CF) is an autosomal recessive disease caused by defects in the CF transmembrane conductance regulator (CFTR) protein. Due to the genetic nature of the disease, interventions in the genome can target any underlying alterations and potentially provide permanent disease resolution. The current development of gene-editing tools, such as designer nuclease technology capable of genome correction, holds great promise for both CF and other genetic diseases. In recent years, Cas9-based technologies have enabled the generation of genetically defined human stem cell and disease models based on induced pluripotent stem cells (iPSC). In this article, we outline the potential and possibilities of using CRISPR/Cas9-based gene-editing technology in CF modeling.

FOOTPRINTS study protocol: rationale and methodology of a 3-year longitudinal observational study to phenotype patients with COPD.

INTRODUCTION: A better understanding is needed of the different phenotypes that exist for patients with chronic obstructive pulmonary disease (COPD), their relationship with the pathogenesis of COPD and how they may affect disease progression. Biomarkers, including those associated with emphysema, may assist in characterising patients and in predicting and monitoring the course of disease. The FOOTPRINTS study (study 352.2069) aims to identify biomarkers associated with emphysema, over a 3-year period. METHODS AND ANALYSIS: The FOOTPRINTS study is a prospective, longitudinal, multinational (12 countries), multicentre (51 sites) biomarker study, which has enrolled a total of 463 ex-smokers, including subjects without airflow limitation (as defined by the 2015 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy report), patients with COPD across the GOLD stages 1-3 and patients with COPD and alpha1-antitrypsin deficiency. The study has an observational period lasting 156 weeks that includes seven site visits and additional phone interviews. Biomarkers in blood and sputum, imaging data (CT and magnetic resonance), clinical parameters, medical events of special interest and safety are being assessed at regular visits. Disease progression based on biomarker values and COPD phenotypes are being assessed using multivariate statistical prediction models. ETHICS AND DISSEMINATION: The study protocol was approved by the authorities and ethics committees/institutional review boards of the respective institutions where applicable, which included study sites in Belgium, Canada, Denmark, Finland, Germany, Japan, Korea, Poland, Spain, Sweden, UK and USA; written informed consent has been obtained from all study participants. Ethics committee approval was obtained for all participating sites prior to enrolment of the study participants. The study results will be reported in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT02719184.

E-cigarette use among young adults in Poland: Prevalence and characteristics of e-cigarette users.

PURPOSE: Electronic cigarette (e-cigarette) use is one of the most popular alternatives to conventional cigarette smoking. This study aimed to investigate the prevalence of cigarette and e-cigarette use among university students from Poland, with particular emphasis on ever and current cigarette and e-cigarette use as well as smoking initiation age. PATIENTS AND METHODS: A cross-sectional survey was conducted between 2017 and 2018 in a group of university students in 5 academic centers in Poland. The questionnaire addressed 46 questions about personal attitudes toward cigarette smoking and e-cigarette use. RESULTS: Data were collected from 7324 participants (67.3% females, aged 21.9 ± 2.1 years), with an overall response rate of 70.1%. Among participants, 71.2% had ever smoked a cigarette, and almost half of the respondents (45%) declared ever use of an e-cigarette. The mean age of first use of a cigarette was significantly lower (16.5 ± 2.5 y-old) than of an e-cigarette (18.6 ± 2.2 y-old; p < 0.001). Exclusive cigarette smoking was declared by 12.9%, 1.3% were e-cigarette users and 1.5% were dual users. Those in the medical field were less likely to try e-cigarettes (odds ratio, OR = 0.73) or to currently smoke conventional cigarettes (OR = 0.82). Older participants were more likely to have ever smoked conventional cigarettes (OR = 1.06), but less likely to have ever used e-cigarettes (OR = 0.88). CONCLUSIONS: In this study, we found a high proportion of young adults who have tried e-cigarettes with both regional and demographic differences. The education profile influences cigarette smoking and e-cigarette use behaviors.

AMPLIFY: a randomized, Phase III study evaluating the efficacy and safety of aclidinium/formoterol vs monocomponents and tiotropium in patients with moderate-to-very severe symptomatic COPD.

Background: AMPLIFY assessed the efficacy and safety of aclidinium bromide/formoterol fumarate (AB/FF) vs its monocomponents and tiotropium (TIO) in patients with moderate-to-very severe symptomatic COPD (NCT02796677). Methods: In this 24-week, Phase III, double-dummy, active-controlled study, symptomatic patients (COPD Assessment Test score ≥10) were randomized to twice-daily AB/FF 400/12 µg, AB 400 µg, or FF 12 µg, or once-daily TIO 18 µg. Co-primary endpoints were change from baseline at week 24 in 1-hour morning post-dose FEV1 (AB/FF vs AB) and in pre-dose (trough) FEV1 (AB/FF vs FF). Non-inferiority of AB vs TIO in pre-dose FEV1 was also an objective. Normalized area under the curve (AUC)0-3/3 h FEV1 and nighttime and early morning symptoms were also assessed. A subgroup participated in a 24-hour serial spirometry sub-study. Results: A total of 1,594 patients were randomized; 566 entered the sub-study. At week 24, 1-hour post-dose FEV1 significantly improved with AB/FF vs AB, FF, and TIO (84, 84, and 92 mL; all P<0.0001). AB/FF significantly improved trough FEV1 vs FF (55 mL, P<0.001) and AB was non-inferior to TIO. AB/FF significantly improved AUC0-3/3 h FEV1 vs all comparators (P<0.0001) and provided significant improvements in early morning symptoms vs TIO. The 24-hour spirometry demonstrated significantly greater improvements with AB/FF in AUC12-24/12 h vs all comparators, and in AUC0-24/24 h vs FF or TIO at week 24. Conclusion: In patients with moderate-to-very severe symptomatic COPD, twice-daily AB/FF significantly improved lung function vs monocomponents and TIO, and early morning symptom control vs TIO.

Estimates of Medication Expenditure for Ischemic Heart Disease Accompanying Chronic Obstructive Pulmonary Disease.

Ischemic heart disease (IHD) is a frequent accompaniment of chronic obstructive pulmonary disease (COPD). Co-occurrence of these two diseases is associated with many risk factors, difficulties in implementing appropriate therapies, numerous complications, and high spending for treatment. All these elements significantly reduce the quality of life of patients. The aim of this study was to estimate the expenditure for medications involved with IHD pharmacotherapy in the course of COPD. This retrospective study was based on the review of medical files of 57 patients, 27 women and 30 men, diagnosed with IHD, according to the severity classification, in the course of COPD which was staged according to the GOLD criteria. We found a considerable increase in per capita per year retail spending for drugs. The spending increased with the severity class of IHD; from 27.41 EUR in Class I to 142.30 EUR in Class IV. This spending did not include the treatment cost for the basic disease, i.e., COPD. A high individual cost burden was decreased by a discounting intervention of the National Health Fund. Despite a relatively high drug expenditure, we consider the treatment being cost-effective since we noticed a reduction in the classical risk factors for IHD, related to metabolic disturbances and lifestyle features, as soon as 2 months after treatment initiation. This study confirms that heart disease accompanying COPD is a frequent occurrence, generating high costs of treatment, which relates to the severity of this comorbidity.

[Treatment of chronic obstructive pulmonary disease--traditional bronchodilatation and targeted anti-inflammatory therapy]. / Leczenie przewleklej obturacyjnej choroby pluc--bronchodylatacja i przeciwzapalna farmakoterapia celowana.

Currently available pharmacological treatment of COPD relies mostly on prophylaxis (smoking cessation) and symptomatic treatment, i.e. inhaled anticholinergic agents, ß2-agonists and phosphodiesterase inhibitors, aiming in their bronchodilatation capacity. Inhaled corticosteroid therapy is mainly prescribed in far advanced stages of the disease and its role in disease modification is still controversial. The authors analize currently available treatment modalities with regards to their potential anti-inflammatory and pleiotropic mode of action, which may lead to disease course modification.

Lung mass in a 28-year-old male: a case report of a rare tumor.

A twenty eight-year-old male presented with a two week history of dyspnea, cough, hemoptysis, chest pain, and fever 38-39°C. He also complained of loss of appetite, general weakness and left leg pain for two months preceding admission. He was referred with suspicion of lung tumor to our institution. Chest X-ray showed almost total atelectasis of the right lung with compensatory overinflation of the contralateral lung. Using computed tomography (CT), a lesion of diameter of 19.3 x 14.1 x 19.1 cm in the right lung, pleuritis, Th3 osteolysis, and compensatory overinflation of the left lung was seen. Bronchoscopy revealed a total obstruction of the right main bronchus due to submucosal infiltration and compression of the right main bronchus with negative histology of bronchial biopsy specimens. Transthoracic fine needle aspiration revealed celullae suspectae probabiliter neoplasmaticae suggesting tumor fusocellularis. USG of the abdomen revealed liver with numerous heterogeneous, solid areas hypo- and hyperechogenic, some of them with features of liquid or the disintegration up to diameter of 74 mm. Subsequent fine needle aspirations of the thorax and liver revealed fibrolamellar hepatocarcinoma and carcinoma adenoides of the lung. Patient underwent chemotherapy with 5-FU/DDP/VCR with no response. This report presents a case of a rare lung metastasis from FL-HCC.

Churg-Strauss syndrome: a case report.

A fifty-year-old female presented with a one month history of progressive dyspnea, productive cough, pain of elbows and knees, and 40°C fever despite antibiotic treatment. She has been diagnosed of bronchial asthma over 25 years before admission and oral and depot glucocorticosteroids as a long-term therapy was applied. Recently, an attempt of inhaled corticosteroids and LABA treatment was introduced with no success. Four years before admission she also developed peripheral neuropathy. Physical examination revealed tachypnea, wheezes, rhonchi and wet cracles on auscultation, tachy?cardia, skin nodules, urticarial rash and necrotic bullae all over the body. Chest X-ray showed transient, patchy, nonsegmental areas of consolidation with predilection for lower zones with the area of consolidation in lower left zone. Obstruction was found on spirometry. Tachy?cardia on ECG and myocardial fluid on ECHO were also detected. Lab exams revealed elevated CRP, WBC, eosinophils, and IgE levels. ANA and ANCA antibodies were not found. Patient was diagnosed of Churg Strauss Syndrome and initial treatment of prednisone was introduced. After four days of treatment, temperature normalized, and dyspnea diminished. After one month of therapy skin lesions regressed. After 18 months of the treatment patient reports no signs, nor symptoms of the disease. Patient continues oral corticosteroid therapy.

[Stenting central airways with tracheobronchial stents]. / Protezowanie tchawicy i duzych oskrzeli z zastosowaniem stentów tchawiczo-oskrzelowych.

Tracheobronchial stenting is indicated in the palliative care of cancer patients with central airways obstruction due to primary chest and neck tumors, metastatic and congenital lesions of these organs. Stents, tubular prostheses, solid or wired, removable or not, of different shape, size, material, are used to treat airway obstructions due to endobronchial overgrowing, infiltration, compression, or relaxation of the airway walls. Silicone stents are well tolerated and removable. Their limitations are: the mucociliary clearance impairment, thick walls, displacement possibility. Rigid bronchoscopy is required for insertion of the prosthesis. Metal stents allow mucociliary transport, exactly match the trachea or bronchus dimension and are insertable with the bronchofiberscope. Attempts of self-absorbed stents application in the course of tracheobronchomalacia and post surgical bronchial wall collapse are being made. The choice of the type of the stent used is made on the basis of personnel experience, type and localisation of the obstruction, clinical status and accompanying diseases.

[Pathogenesis of chronic obstructive pulmonary disease. Molecular mechanisms (part II)]. / Patogeneza przewleklej obturacyjnej choroby pluc. Czesc II. Podloze molekularne.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Smoking is considered the major cause of the disease. Relatively little is known about the molecular mechanisms underlying inflammatory response in smokers' lungs and how this relates to the susceptibility to the disease, particularly why only 10-15% of smokers develop COPD. Recent development in molecular biology techniques allowed the insight into the inner space of the cell, to the levels far beyond the reach of the traditional methods. We review recent hypotheses on cellular and molecular background of COPD with emphasis on the potential role of histone acetylation, as a key modulator of enhanced gene transcription responsible for proinflammatory cytokines production in COPD. Authors propose a role for modification of nucleosomal structure in inflammatory cytokine gene transcription in response to smoking. Cigarette smoke causes oxidative stress altering the balance between histone deacetylation and acetylation in favor of acetylation. This can contribute to the airflow obstruction in smokers susceptible to the development of COPD. Furthermore, histone acetylation seems to be a potential mechanism exclusive to smokers with susceptibility to COPD based on the transcription of specific pro- and anti-inflammatory cytokine combinations.

[Pathogenesis of chronic obstructive pulmonary disease. Cellular mechanisms (part I)]. / Patogeneza przewleklej obturacyjnej choroby pluc. Czesc i. podloze komórkowe.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Smoking is considered the major cause of the disease. All smokers develop airway inflammation through oxidative stress with macrophages, neutrophiles, lymphocytes, eosinophils, NK-cells and mediators involved. Macrophages through the activation of Nuclear Factor kappa B (NF.-kappaB) release proinflammatory mediators, lymphocyte chemotactic agents and elastolytic enzymes, activate neutrophil driven serine proteases and GM-CSF. Neutrophiles release IL-8 which in turn recruits neutrophils to the airways. In response to cigarette smoke lung epithelium may release TNF-alpha, TGF-beta, IL-1beta, GM-CSF, IL-8 reactive oxygen species (ROS). Increased number of lymphocyte T CD8+ and CD4+ subpopulations may lead to lung epithelium cells apoptosis and necrosis through perphorines and granzyme-B and TNF-alpha activation. Moreover, increased expression of IL-6, IL-10, IL-12, IL-13, and INF-gamma is observed. Authors indicate the possibility of new treatment strategies such as: agents directed against adhesion molecules, chemokines, phosphodiesterase 4, p38 MAPK, NF.-kappaB phosphoinositide-3-kinase gamma, TGF-beta, NOS synthase, serine proteinases and matrix metalloproteinases.

p53 N-terminal Ser-15 approximately P and Ser-20 approximately P levels in squamous cell lung cancer after radio/chemotherapy.

Functional regulation of p53 protein, a critical regulator of cell cycle and apoptosis, was investigated in fiberoptic bronchoscopy biopsy samples taken from 23 patients suffering from recurrent squamous cell lung cancer by analyzing the expression and phosphorylation status of the p53 at Ser15 and Ser20 before and after treatment with radiotherapy/cisplatin/vinorelbine. Poly(ADP-ribose) levels as a marker of cellular DNA damage, expression of wild-type and mutated p53 protein, and Ki-67 expression as a marker of proliferation was also determined. Median p53 expression increased (61% increase) after therapy. p53 phosphorylated on Ser20 was also increased by approximately 57% in radiotherapy/chemotherapy patients, and these changes correlated with Ki-67 proliferation and with elevated (by 69%; P < 0.01) poly(ADP-ribose) levels. Our data indicate that apart from changes in p53 quantity, post-translational phosphorylation/dephosphorylation-mediated alterations, especially at Ser20 may play a role in p53 stabilization and, therefore, in antiproliferative activity of drugs inducing DNA damage and apoptosis.

[Comparison of cellular composition of induced sputum, bronchial washings and bronchoalveolar lavage fluid in sarcoidosis, hypersensitivity pneumonitis and COPD]. / Porównanie skladu komórkowego indukowanej plwociny, popluczyn oskrzelowych i plynu z plukania oskrzelowo-pecherzykowego w sarkoidozie, alergicznym zewnatrzpochodnym zapaleniu pecherzyków plucnych i przewleklej obturacyjnej chorobie pluc.

UNLABELLED: This study compares the cellular profiles of induced sputum (IS), bronchial washing (BW), and BAL fluid (BAL) in newly diagnosed sarcoidosis (BBS) and hypersensitivity pneumonitis (HP) patients to COPD group, and examines whether inflammatory cell counts from IS correlated with inflammatory cell counts from BW and BAL in sarcoidosis and HP patients. METHODS: We recruited 23 untreated patients with stage II pulmonary sarcoidosis, 15 untreated patients with HP and 17 COPD patients. Sputum was induced with hypertonic saline solution in all individuals. Bronchoscopy was performed on a different occasions in all patients. RESULTS: Mean lymphocyte counts in IS, BW, and BAL fluid from sarcoidosis and HP patients were significantly higher than in COPD subjects (8.9% and 13.8 vs 2.9%, p < 0.05; 11.9% and 30.5 vs 3.2%, p < 0.05; 21.5% and 56 vs 3.4%, p < 0.05, respectively). Moreover we found higher percentage of CD4+, CD3+ CD28+, CD3+ HLADRV+, and gamma delta T cells in IS, BW, and BAL fluid from both BBS and HP groups than in from COPD. Elevated CD4/CD8 ratio characterized IS, BW and BAL fluid in BBS group. Strong correlation IS/BAL and IS/BW of CD3+ CD28+, CD3+ HLADRV+, and CD4/CD8 ratio was found. CONCLUSIONS: We demonstrated that, although the relative proportion of inflammatory cells differed in the three samples, lymphocyte counts in IS were high. This finding suggests that IS could be used as a valuable alternative method to more conventional invasive techniques in clinical assessment of interstitial lung diseases patients.