Natural Killer Cells as a Further Insight into the Course of Chronic Obstructive Pulmonary Disease.

The role of natural killer (NK) cells in chronic obstructive pulmonary disease (COPD) pathogenesis has been discussed but is not yet clearly understood. This current study aimed to evaluate the associations between immunophenotypes, degrees of maturity, and the expression level of functional receptors of NK cells in the lung environment present in bronchoalveolar lavage fluid (BALF), and an attempt was made to determine their relationship in the course and progression of COPD. A total of 15 COPD patients and 14 healthy smokers were included. The clinical parameters of COPD were evaluated. In both groups, NK cells using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry were assessed in the peripheral blood. Additionally, NK cells using the same method were assessed in BALF in the COPD subgroup. The blood's NK cells differed from the estimated group's maturity and receptor expression. Functional receptors CD158b+, CD314+, and CD336+ expressed by NK cells were significantly interlinked with age, RV, TLC, 6MWT, smoking, and the number of exacerbations. These results confirm the essential role of NK cells in COPD pathogenesis. Additionally, the relationship between clinical parameters and NK cell expression may indicate its participation in the disease progression and exacerbation and allow for a better understanding of NK cell biology in COPD.

Deep learning algorithm for visual quality assessment of the spirograms.

Objective. The quality of spirometry manoeuvres is crucial for correctly interpreting the values of spirometry parameters. A fundamental guideline for proper quality assessment is the American Thoracic Society and European Respiratory Society (ATS/ERS) Standards for spirometry, updated in 2019, which describe several start-of-test and end-of-test criteria which can be assessed automatically. However, the spirometry standards also require a visual evaluation of the spirometry curve to determine the spirograms' acceptability or usability. In this study, we present an automatic algorithm based on a convolutional neural network (CNN) for quality assessment of the spirometry curves as an alternative to manual verification performed by specialists.Approach. The algorithm for automatic assessment of spirometry measurements was created using a set of randomly selected 1998 spirograms which met all quantitative criteria defined by ATS/ERS Standards. Each spirogram was annotated as 'confirm' (remaining acceptable or usable status) or 'reject' (change the status to unacceptable) by four pulmonologists, separately for FEV1 and FVC parameters. The database was split into a training (80%) and test set (20%) for developing the CNN classification algorithm. The algorithm was optimised using a cross-validation method.Main results. The accuracy, sensitivity and specificity obtained for the algorithm were 92.6%, 93.1% and 90.0% for FEV1 and 94.1%, 95.6% and 88.3% for FVC, respectively.Significance.The algorithm provides an opportunity to significantly improve the quality of spirometry tests, especially during unsupervised spirometry. It can also serve as an additional tool in clinical trials to quickly assess the quality of a large group of tests.

"Current place of impulse oscillometry in the assessment of pulmonary diseases."

In 1956, a diagnostic tool using the forced oscillation technique (FOT) was developed to examine respiratory functions. A modification of this method is impulse oscillometry (IOS). In the latter, a loudspeaker delivers to the respiratory system a regular, square pressure wave at a constant frequency from which all other individual frequencies are derived using spectral analysis. The usefulness of IOS has been examined in relation to COPD, asthma, interstitial lung diseases, obstructive sleep apnea, and other conditions. The greatest advantage, most notable in children, is the ability to monitor the course of a disease and to assess the response to therapy in a simple way, i.e., minimal requirements for the cooperation of the patient, rapid and reproducible measurements. The IOS shows similar or even higher sensitivity than spirometry in detecting small airways dysfunction (SAD). The most well-known result observed in peripheral airways disease (PAD) is the frequency dependence of resistance. Importantly, the abnormal resistance at a specific frequency may occur with normal spirometry in those with early PAD. Moreover, IOS is particularly useful if the patient cannot perform effort dependent exhalation. Despite its advantages, the technique is still poorly found in official worldwide recommendations. Nonetheless, considering the promising results of many studies, an increase in interest in IOS is expected, and it could soon be on par with standard pulmonary function tests. The aim of this work is to present the basics, current views, and various aspects of IOS. To carry out our analysis, we searched for relevant publications on PubMed, Web of Science. Original and review articles were selected and discussed.

Cardiovascular Function in Obstructive Sleep Apnea Patients with Controlled Hypertension.

This study investigated hemodynamic characteristics of obstructive sleep apnea (OSA) accompanied by hypertensive disease in obese men, in whom blood pressure was pharmacologically controlled within the normal range, not exceeding 140/90 mmHg. There were 21 severe OSA patients (mean age 54.1 ± 9.3 years, apnea-hypopnea index of 47.1 ± 18.8 episodes per hour) included in the study, in whom OSA was diagnosed with polysomnography. The control group consisted of healthy normotensive age-matched subjects. Hemodynamic profile was recorded nonivasively with impedance cardiography. Brachial blood pressure and radial artery tonometry were performed to capture and reconstruct peripheral radial and central aortic pressure waveforms in both groups of subjects. Compared to healthy men, OSA patients had a significantly higher body mass index (BMI); the mean increase in BMI amounted to 6.4 ± 1.2 kg/m2. The patients also presented significant differences in the hemodynamic profile. The difference consisted of a faster heart rate, higher peripheral pulse pressure, and reduced blood flow acceleration and velocity indices, describing myocardial contractility. Notably, the significance of hemodynamic differences in OSA patients disappeared in the analysis adjusted for the outstanding increase in BMI. In conclusion, the findings strongly suggest that obesity rather than the hypertensive disease per se is a source of hemodynamic consequences in OSA patients.

Comorbidities in chronic obstructive pulmonary disease: Results of a national multicenter research project.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with various comorbidities, which influence the course of COPD and worsen prognosis. OBJECTIVES: The aim of this study was to analyze the comorbidities in a cohort of COPD patients in Poland during 12 months of observation. MATERIAL AND METHODS: A total of 444 COPD patients (median age: 66.1 years) in all stages of airflow limitation severity were enrolled. Medical histories and a questionnaire concerning comorbidities were analyzed at baseline and after 12 months (data of 267 patients available). Anthropometric data, pulmonary function, and body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE index) were assessed. RESULTS: No comorbidities were reported in 9 patients (2.0%), 101 patients (22.7%) had 1-2 comorbidities, 243 (54.7%) had 3-5, and 91 (20.6%) had more than 5 comorbidities. Cardiovascular diseases (CVDs) were the most frequent ones, followed by peptic ulcer, obstructive sleep apnea (OSA), diabetes, gastroesophageal reflux disease (GERD), and osteoporosis; 11 patients had a history of lung cancer. Cachexia was observed in 11 cases, overweight in 136 cases and obesity in 139 cases. The incidence of CVDs increased with time. The number of comorbidities correlated with the body mass index (BMI) and the number of hospitalizations for extra-pulmonary causes, but not with airflow limitation. The BODE index score increased with the number of comorbidities. CONCLUSIONS: In a cohort of Polish COPD patients, the most frequent comorbidities were CVDs. The number of comorbidities affected the BODE index, but not airflow limitation. The BODE index is better than forced expiratory volume in 1 s (FEV1) in the rating of COPD patients' condition. The BMI correlated with the number of comorbidities as well as the number of hospitalizations for extra-pulmonary causes.

COPD Course and Comorbidities: Are There Gender Differences?

The prevalence of chronic obstructive pulmonary disease (COPD) has increased more rapidly in women than in men during the past two decades. Clinical presentation, comorbidities and prognosis may differ between genders and may influence management decisions. The influence of gender on COPD expression has not been clearly explained to date. Thus, the aim of this study was to evaluate significant differences between women and men suffering from COPD, regarding clinical presentation, pulmonary function test results, comorbidities, and prognosis. We prospectively recruited 470 patients with stable COPD with a history of smoking (152 women, 318 men, mean age 65.5 ± 8.8 vs. 66.6 ± 9.4 years, respectively). Comorbidities and exacerbations were recorded. Spirometry, body plethysmography, carbon monoxide diffusing capacity and 6-min walk tests were performed. The BODE prognostic score was also calculated. We found that women smoked less in comparison to men (30.4 vs. 41.9 pack-years, p < 0.05), showed more exacerbations (2.5 vs. 1.7, p = 0.01), higher forced expiratory volume in 1 s (FEV1%predicted), and increased residual volume/total lung capacity (RV/%TLC), but they had the same intensity of dyspnea. Women showed fewer comorbidities, on average, per patient (5.4 vs. 6.4, p = 0.002), but had a higher prevalence of at least seven comorbidities per patient (48.7% of women vs. 33.0% of men, p < 0.05). Women also had a significantly worse prognosis (4.6 vs. 3.1 BODE score, p < 0.05) that correlated with the number of comorbidities (r = 0.33, p < 0.01). In conclusion, this study strongly supports the existence of different gender phenotypes in COPD, especially regarding exacerbations, comorbidities, and prognosis. The gender difference may indicate a need for a targeted assessment and management of COPD in women and men.

Airway Obstruction in Sleep Apnea Patients.

Obstructive sleep apnea (OSA) is a condition of breathing pathology occurring during sleep, characterized by repeated episodes of upper airway obstruction. The aim of the study was to determine the occurrence of airway obstruction in smoking males with OSA in whom lung function tests had not been performed before. One hundred and four current smokers selected from 1241 patients were enrolled for the research. The subjects included in the study smoked minimum 20 cigarettes a day for at least 10 years. The diagnosis of OSA was confirmed by polysomnography (PSG) in the Sleep Laboratory and subjects were assigned to one of three groups, depending on the severity of OSA. The control group consisted of 30 age-matched male smokers in whom OSA was not confirmed in PSG. Patients from the study and control group scored ≥ 11points in the Epworth Sleepiness Scale. Spirometry, impulse oscillometry, and body plethysmography were used to assess pulmonary function. Airflow limitation in subjects of the control group and OSA patients was confirmed. There were no significant differences in the incidence of bronchial obstruction between the control and study groups, and among the patients of various OSA severity. We conclude that the severity of OSA in smokers does not associate with the presence of airway obstruction. However, the increased peripheral respiratory resistance found in oscillometry did relate to a longer smoking time in OSA patients.

Molecules of Damage-Associated Patterns in Bronchoalveolar Lavage Fluid and Serum in Chronic Obstructive Pulmonary Disease.

Chronic exposure to detrimental environmental factors may induce immunogenic cell death of structural airway cells in chronic obstructive pulmonary disease (COPD). Damage-associated molecular patterns (DAMPs) is a family of heterogeneous molecules released from injured or dead cells, which activate innate and adaptive immune responses on binding to the pattern recognition receptors on cells. This study seeks to define the content of DAMPs in the bronchoalveolar lavage fluid (BALF) and serum of COPD patients, and the possible association of these molecules with clinical disease features. Thirty COPD in advanced disease stages were enrolled into the study. Pulmonary function tests, arterial blood gas content, 6-minute walk test, and BODE index were assessed. The content of DAMPs was estimated using the commercial sandwich-ELISA kits. We found differential alterations in the content of various DAMP molecules. In the main, BALF DAMPs positively associated with age, forced expiratory volume in one second (FEV1), and residual volume (RV); and inversely with PaO2, residual volume/total lung capacity (RV/TLC) ratio, and the disease severity staging. In serum, DAMPS positively associated with the intensity of smoking and inversely with age, PaO2, and TLC. In conclusion, DAMPs are present in both BALF and serum of COPD patients, which points to enhanced both local in the lung environment as well as systemic pro-inflammatory vein in this disease. These molecules appear involved with the lung damage and clinical variables featuring COPD. However, since the involvement of various DAMPs in COPD is variable, the exact role they play is by far unsettled and is open to further exploration.

Distribution and characteristics of COPD phenotypes - results from the Polish sub-cohort of the POPE study.

Background: This study aimed to examine the distribution of predefined phenotypes, demographic data, clinical outcomes, and treatment of patients who were included in the Polish cohort of the Phenotypes of COPD in Central and Eastern Europe (POPE) study. Patients and methods: This was a sub-analysis of the data from the Polish cohort of the POPE study, an international, multicenter, observational cross-sectional survey of COPD patients in Central and Eastern European countries. The study included patients aged >40 years, with a confirmed diagnosis of COPD, and absence of exacerbation for at least 4 weeks before study inclusion. A total of seven Polish centers participated in the study. Results: Among the 430 Polish COPD patients enrolled in the study, 61.6% were non-exacerbators (NON-AE), 25.3% were frequent exacerbators with chronic bronchitis (AE CB), 7.9% were frequent exacerbators without chronic bronchitis (AE NON-CB), and 5.1% met the definition of asthma-COPD overlap syndrome (ACOS). There were statistically significant differences among these phenotypes in terms of symptom load, lung function, comorbidities, and treatment. Patients with the AE CB phenotype were most symptomatic with worse lung function, and more frequently reported anxiety and depression. Patients with the ACOS phenotype were significantly younger and were diagnosed with COPD earlier than those with other COPD phenotypes; those with the ACOS phenotype were also more often atopic and obese. Conclusion: There is significant heterogeneity among COPD patients in the Polish population in terms of phenotype and clinical outcome. The non-exacerbator phenotype is observed most frequently in Poland, while the frequent exacerbator with chronic bronchitis phenotype is the most symptomatic.

Body Composition, Anthropometric Indices and Hydration Status of Obstructive Sleep Apnea Patients: Can Cachexia Coexist with Obesity?

The aim of this study was to elucidate body composition, anthropometric indices, and hydration status in obstructive sleep apnea (OSA) patients, taking into account different disease stages, gender, and the possibility of the presence of cachexia. There were 98 OSA patients and 23 control subjects enrolled into the study. All study participants underwent polysomnography examination. Body mass index (BMI), fat mass index (FMI), fat free mass, muscle mass, body cell mass, total body water, and extracellular and intracellular water were evaluated. The neck, abdominal, and waist circumference was measured. We found that overweight and obesity were present in 96% of patients. Cachexia was present in one OSA individual with comorbidities. Apnea-hypopnea index correlated with the neck and waist circumference, and with BMI in OSA patients. All muscle indices and water contents above outlined were significantly higher in severe OSA compared with control subjects. BMI, FMI, neck circumference, and extracellular water were greater in a subset of severe OSA compared with a moderate OSA stage. The female OSA patients had a higher FMI than that present in males at a comparable BMI. We conclude that the most body composition indices differed significantly between severe OSA patients and control subjects. A higher FMI in females at a comparable BMI could be due to a discordance between BMI and FMI. Cachexia occurs rarely in OSA and seems to coexist with comorbidities.

Myeloid­derived suppressor cells in bronchoalveolar lavage fluid in patients with chronic obstructive pulmonary disease.

INTRODUCTION Myeloid­derived suppressor cells (MDSCs) have the potent ability to suppress T­cell function, and are important in the regulation of chronic inflammation and carcinogenesis. MDSCs may influence local and systemic inflammation and carcinogenesis in COPD; however, their presence in bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) or their relationship with clinical parameters in COPD has not been studied yet. OBJECTIVES The aim of the study was to assess MDSCs in BALF and PB and to analyze the relationship between MDSCs and clinical parameters in COPD. PATIENTS AND METHODS The study included 64 patients with stable COPD. The clinical parameters of the patients were studied, and MDSCs were assessed using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry. RESULTS The percentage of MDSCs in BALF was lower than that in PB (0.63 ±0.90 vs 3.94 ±0.38). In BALF, MDSCs (% of mononuclear cells) correlated with forced expiratory volume in 1 second (rs = -0.30, P = 0.0185), residual volume/total lung capacity (rs = 0.32, P = 0.0148), PaO2 (rs = -0.45, P = 0.0002), arterial oxygen saturation (SaO2; rs = -0.41, P = 0.0008), and diffusion capacity of carbon dioxide (rs = -0.32, P = 0.0211). There was a significant negative correlation between MDSCs (% of all leukocytes) and arterial oxygen pressure (rs = -0.42, P = 0.0006) and SaO2 (rs = -0.37, P = 0.0027). No correlations were found in PB. CONCLUSIONS MDSCs are present in human lung microenvironment and may be involved in local inflammation in COPD. Future studies should focus on a detailed assessment of MDSCs in local and systemic inflammation in COPD.

Serum levels of apoptosis-related markers (sFasL, TNF-a, p53 and bcl-2) in COPD patients.

INTRODUCTION: Taking into account important role of apoptosis in COPD pathogenesis, we wanted to asses the serum levels of markers involved in apoptosis regulation, including apoptosis inducers such as TNF-a, sFasL or p53 protein and apoptosis inhibitor bcl-2 and, in addition, to compare these markers with selected COPD parameters. MATERIAL AND METHODS: In 181 patients (60 women) with COPD (age was 62.2+ 9.37 years; FEV1% 55.2 + 19.98 %) and in 29 controls (11 women), serum levels of TNF-a, sFasL, p53 and bcl-2 were evaluated by the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: In COPD patients the mean sFasL level was 0.092 ± 0.077 ng/ml and mean TNF-a level was 2.911 ± 3.239 pg/ml. There were no differences in serum sFasL and TNF-a in COPD patients and control group. TNF-a and sFasL did not correlate with COPD parameters such as FEV1%, BMI, RV% (percentage of predicted value of residual volume) or BODE. Although we tried to evaluate bcl-2 and p53 protein serum levels with two different tests, measurable levels of bcl-2 were only detected in 15 patients and p53 in only 3 patients. Bcl-2 values were from 0.418 to 11.423 ng/ml and p53 from 90.772 to 994.749 pg/ml. CONCLUSIONS: We didn't observe any differences in serum levels of pro- and antiapoptotic markers in COPD patients and the control group or correlations between the markers studied and COPD parameters.

Susceptibility loci in lung cancer and COPD: association of IREB2 and FAM13A with pulmonary diseases.

Genome-wide association studies have identified loci at 15q25 (IREB2) and 4q22 (FAM13A), associated with lung cancer (LC) and chronic obstructive pulmonary disease (COPD). The aim of our research was to determine the association of IREB2 and FAM13A SNPs with LC and severe/very severe COPD patients. We examined IREB2 variants (rs2568494, rs2656069, rs10851906, rs13180) and FAM13A (rs1903003, rs7671167, rs2869967) among 1.141 participants (468 LC, 149 COPD, 524 smoking controls). The frequency of the minor IREB2 rs2568494 AA genotype, was higher in LC vs controls (P = 0.0081, OR = 1.682). The FAM13A rs2869967 was associated with COPD (minor CC genotype: P = 0.0007, OR = 2.414). The rs1903003, rs7671167 FAM13A variants confer a protective effect on COPD (both P < 0.002, OR < 0.405). Haplotype-based tests identified an association of the IREB2 AAAT haplotype with LC (P = 0.0021, OR = 1.513) and FAM13A TTC with COPD (P = 0.0013, OR = 1.822). Cumulative genetic risk score analyses (CGRS), derived by adding risk alleles, revealed that the risk for COPD increased with the growing number of the FAM13A risk alleles. OR (95% CI) for carriers of ≥5 risk alleles reached 2.998 (1.8 to 4.97) compared to the controls. This study confirms that the IREB2 variants contribute to an increased risk of LC, whereas FAM13A predisposes to increased susceptibility to COPD.

[Chronic obstructive pulmonary disease and cardiovascular diseases--'cardiopulmonary continuum']. / Przewlekla obturacyjna choroba pluc i choroby sercowo-naczyniowe--"kontinuum sercowo-plucne"

Chronic obstructive pulmonary disease (COPD) is characterised by persistent airflow limitation and extrapulmonary comorbidities, which contribute to the overall severity. Some risk factors, with tobacco smoking as the most serious one, lead to a chronic, systemic inflammation that plays the main role in the pathogenesis of COPD and comorbidities, including cardiovascular diseases (CVD). The course of COPD is diverse; it depends on pathologies in the respiratory system and on other organ dysfunctions. CVDs are the most commonly recognised comorbidities in COPD patients. The severity and natural course of COPD, as well as quality of the patient's life, are influenced by them. CVDs are frequently the reason for hospitalisation and may lead to death. They are also an important prognostic factor. Comorbidities may prolong exacerbation of COPD. On the other hand, COPD is an independent risk factor of CVD. The prevalence of COPD is high in patients suffering from coronary artery disease, and airflow limitation is a major risk factor for chronic heart failure. These complex interactions between heart and lung can be denoted as 'cardiopulmonary continuum'. These dependencies are not recognised in detail. Currently research is being done, which attempts to explain these complicated relations. For many years COPD and CVD were not connected. Today it is known that patients suffering from COPD must be provided comprehensive care. It is necessary to monitor the risk of CVD and their influence on the COPD course. Careful and proper treatment of all diseases is essential. An interdisciplinary team with good cooperation should prepare a plan of COPD treatment with simultaneous therapy of comorbidities.