Paweł Piesiak

Efficacy of Noninvasive Volume Targeted Ventilation in Patients with Chronic Respiratory Failure Due to Kyphoscoliosis

Severe kyphoscoliosis can cause chronic respiratory failure. Noninvasive mechanical ventilation (NIMV) is a new optional treatment for such patients. The aim of this study was to evaluate the effectiveness of average volume-assured pressure support (AVAPS) NIMV in patients with kyphoscoliotic chronic respiratory failure. The study was performed in 12 patients (mean age 49±11 years and body mass index 27.5±7.9 kg/m2) with advanced kyphoscoliosis complicated by severe respiratory failure (PaO2 6.68±0.34 kPa, SaO2 81.7±3.1%, PaCO2 9.51±1.08 kPa) treated by the NIMV. The short-term, after 5 days, and long-term, after 1 year of home treatment, efficacy of NIMV was evaluated. We found a significant improvement of diurnal PaO2 and PaCO2 on the 5th day of NIMV (an increase of 1.4±0.3 kPa and a decrease of 1.8±0.8 kPa, respectively; p<0.05) and after one year NIMV (an increase of 2.07±0.46 kPa and a decrease of 2.68±0.85 kPa, respectively; p<0.05). There was a significant increase of mean blood oxygen saturation during sleep on the 5th day (86.2±3.2%) and after 1 year of treatment (89.4±2.1%) compared with the baseline level (83.2±3.2%). The forced vital capacity also increased after 1 year (1,024±258 ml vs. the baseline 908±267 ml; p<0.05). The NIMV was well tolerated and no patient discontinued the treatment during the observation period. We conclude that AVAPS NIMV is an effective treatment option in kyphoscoliotic patients with chronic respiratory failure, resulting in a prompt and long-term improvement of daytime and nocturnal blood gas exchange.

Bronchial hyper-responsiveness, subepithelial fibrosis, and transforming growth factor-β1 expression in patients with long-standing and recently diagnosed asthma

Introduction:Chronic inflammation in asthmatic airways leads to bronchial hyper-responsiveness (BHR) and the development of structural changes. Important features of remodeling include the formation of subepithelial fibrosis due to increased collagen deposition in the reticular basement membrane. Transforming growth factor (TGF)-β might be a central mediator of tissue fibrosis and remodeling.Materials and Methods:Immunohistochemistry was used to measure collagen III deposition and TGF-β1 expression in biopsies from patients with long-standing asthma treated with inhaled corticosteroids, patients with recently diagnosed asthma, and control subjects. Computer-assisted image analysis was used to evaluate total basement membrane (TBM) thickness.Results:Asthmatics, particularly those with long-standing asthma, had thicker TBMs than healthy subjects. Collagen III deposition was comparable in the studied groups. BHR was not correlated with features of mucosal inflammation and was lower in steroid-treated patients with long-standing asthma than in subjects with newly diagnosed asthma untreated with steroids. Epithelial TGF-β1 expression negatively correlated with collagen III deposition and TBM thickness.Conclusions:The study showed that TBM thickness, but not collagen III deposition, could be a differentiating marker of asthmatics of different disease duration and treatment. The lack of correlation between BHR and features of mucosal inflammation suggests the complexity of BHR development. Corticosteroids can reduce BHR in asthmatics, but it seems to be less effective in reducing subepithelial fibrosis. The role of epithelial TGF-β1 needs to be further investigated since the possibility that it plays a protective and anti-inflammatory role in asthmatic airways cannot be excluded.

Soluble Ligand CD40 and Uric Acid as Markers of Atheromatosis in Patients with Obstructive Sleep Apnea

The aim of the study was to evaluate the risk of atheromatosis in patients with obstructive sleep apnea (OSA), as based on the concentration of the pro-atherogenic soluble CD40L ligand (sCD40L) in relation to the level of uric acid. The serum levels of sCD40L and uric acid were measured in 79 OSA patients (mean apnea/hypopnea index - AHI 34.4 ± 20.9) and in 40 healthy controls. We found that sCD40L was higher in the OSA patients with hyperuricemia than that in the patients with uric acid in the normal range (sCD40L: 9.0 ng/ml vs. 8.0 ng/ml, respectively, p < 0.05). There was a positive association of sCD40L with AHI (p = 0.01) and a negative one with the mean minimal nocturnal SaO₂(p < 0.05). Uric acid correlated negatively with the mean and minimal SaO₂and positively with the oxygen desaturation index (p < 0.05). OSA patients with hyperuricemia also had a higher prevalence of hypertension and ischemic heart disease. We conclude that OSA patients with increased uric acid concentration have increased risk of atheromatosis, as indicated by a higher level of soluble pro-atherogenic ligand CD40, and a higher prevalence of cardiovascular adverse events.

Hypoxemia During Bilevel Positive Airway Pressure Treatment in Patients with Obstructive Sleep Apnea Syndrome and Chronic Respiratory Insufficiency

In patients with obstructive sleep apnea (OSA) syndrome and chronic respiratory insufficiency one of the options of treatment is bilevel positive airway pressure (BPAP) during sleep. The aim of the study was to find out what are the factors influencing the early results of BPAP treatment in such OSA patients. The study was carried out in 55 adult obese patients (mean body mass index 45 ± 7 kg/m(2)), severe OSA syndrome (mean apnea/hypopnea index 62 ± 19), and chronic respiratory insufficiency (mean PaCO(2) 54 ± 5.7 torr) who underwent polysomnography during BPAP treatment. In 31 patients (56%) the mean SaO(2) during sleep was <88% despite the optimal BPAP and oxygen titration: 83 ± 4% during NREM and 81 ± 7% during REM sleep vs. 91 ± 2% and 90 ± 3%, respectively, in the remaining 24 patients (p < 0.001). The patients with advanced hypoxemia during sleep and BPAP treatment had lower forced vital capacity (2.2 ± 0.9 vs. 2.7 ± 0.8 l, p < 0.05), lower diurnal PaO(2) (49 ± 8 vs. 54 ± 7 torr), higher diurnal PaCO(2) (57 ± 5 vs. 52 ± 5 torr, p < 0.01), and higher PaCO(2) during sleep (75 ± 13 vs. 59.5 ± 7.5 torr). In conclusion, in obese patients with severe OSA syndrome and chronic alveolar hypoventilation there is a risk of sleep hypoxemia during BPAP treatment, despite optimal pressure titration.

Correlations between osteoprotegerin serum levels and body composition parameters in patients with sleep apnea syndrome and the possible influence on cardiovascular risk

INTRODUCTION Osteoprotegerin (OPG) is a member of the tumor necrosis factor family and a key regulator in bone turnover; it plays a role in the development of many cardiovascular diseases and may be treated as a marker of vascular damage. Bioelectrical impedance analysis (BIA) is a reliable, non-invasive and effective technique for measuring body composition. The aim of the study was to evaluate correlations between osteoprotegerin serum levels and body composition parameters in sleep apnea patients and their influence on cardiovascular risk. MATERIAL AND METHODS A total of 125 patients with newly diagnosed OSA were enrolled in the study (including 34 females). The mean age was 54.48±8.81 years, mean AHI 33.16±20.44/h and mean BMI 33.76±7.18. A control group comprised 59 healthy subjects with mean age of 51.27±12.97 years and mean BMI 29.47±5.42. All subjects underwent a nocturnal respiratory polygraphy and body composition measurements were taken with bioelectrical impedance analysis. OPG serum levels were measured using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS In OSA patients OPG correlated negatively with muscle mass percentage (MM%), phase angle, fat free mass percentage (FFM%) and body cell mass percentage (BCM%), while there was a positive correlation between osteoprotegerin and fat mass percentage (FM%). We demonstrated higher OPG serum levels in OSA patients with cardiovascular diseases than in those without comorbidities (4.01 vs 3.46pmol/l, p<0.05). CONCLUSION Our findings, combined with previous observations in other diseases, suggest that elevated OPG serum levels together with selected body composition parameters may be helpful in identifying OSA patients with increased cardiovascular risk.

Pulmonary Function Impairment in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

Deterioration of pulmonary function can be the sole symptom of early stages of pulmonary complications following allogeneic hematopoietic cells transplantation (alloHCT). The aim of the study was to evaluate the prevalence and types of pulmonary function abnormalities in allogenic cells recipients. Twenty three (5 children and 18 adults) allogeneic hematopoietic cells recipients who underwent pulmonary function assessment before and 6-12 months after alloHCT were included in the study. Forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), total lung capacity (TLC), and lung diffusion capacity for carbon dioxide (D(L)CO) were determined. Values <80% of predicted were considered abnormal. We found significant reductions of FVC, D(L)CO, and TLC after alloHCT. The most important reduction was noted in D(L)CO (pre-alloHCT of 85%±15% vs. post- alloHCT of 60%  ±  21%, p<  0.05). Six patients (26%) presented with lung function impairment before alloHCT: obstructive lung disease (4%), restrictive lung disease (13%), and decreased D(L)CO (17%). In 19 patients (83%) pulmonary function abnormalities were demonstrated after alloHCT. The most common disturbance was a D(L)CO decrease that occurred in 16 patients (70%). In conclusion, frequency of pulmonary function abnormalities in patients after alloHCT is high. A diffusion capacity decrease and restrictive pattern of ventilation insufficiency develop in the majority of patients after alloHCT. It would be reasonable to include pulmonary function testing to standard periodic examination in patients qualified for, and after, alloHCT procedure.

Efficacy of Noninvasive Mechanical Ventilation in Obese Patients with Chronic Respiratory Failure

Chronic respiratory failure (CRF) develops in a minority of obese patients. Noninvasive mechanical ventilation (NIMV) is a new optional treatment for such patients. The aim of this study was to evaluate the effectiveness of NIMV in obese patients with CRF. The material of the study consisted of 34 obese patients (body mass index 47.3 ± 7.9 kg/m(2)) with CRF (PaO2 = 6.40 ± 0.93 kPa and PaCO2 = 8.67 ± 2.13 kPa) who were hypoxemic despite an optimal therapy. Thirteen patients had an overlap syndrome (OS) - chronic obstructive pulmonary disease (COPD) coexisting with obstructive sleep apnea syndrome (OSAS) and 21 patients had obesity-hypoventilation syndrome (OHS). Ventilation parameters were determined during polysomnography. The efficacy of NIMV was evaluated on the fifth day and after 1 years home treatment. We observed a significant increase in the mean blood oxygen saturation during sleep in all patients; the increase was greater in patients with OHS (92.6 ± 1.4 %) than in patients with OS (90.4 ± 1.8 %). There was a significant improvement of diurnal PaO2 and PaCO2 on the fifth day of NIMV (mean PaO2 increase 2.1 kPa and PaCO2 decrease 0.9 kPa) and also after 1 year of home NIMV (mean PaO2 increase 1.9 kPa and PaCO2 decrease 2.4 kPa). Only one patient stopped treatment because of lack of tolerance during the observation period (1-3 years). In conclusion, NIMV is an effective and well tolerated treatment option in obese patients with CRF resulting in a rapid relief of respiratory disorders during sleep and a gradual, long-term improvement of gas exchange during the day, particularly in patients with OHS.

Genotyping of Pneumocystis jirovecii in colonized patients with various pulmonary diseases

Pneumocystis jirovecii is an opportunistic fungus causing Pneumocystis pneumonia primarily in immunosuppressed patients. However, immunocompetent individuals may become colonized and, as asymptomatic carriers, serve as reservoirs of the pathogen. Moreover, these asymptomatic carriers are at higher risk of developing pneumonia if favorable conditions occur. This study aimed to determine the prevalence of P. jirovecii in patients with various pulmonary diseases and to characterize the genetic diversity of organisms circulating in the studied population. Bronchial washing specimens from 105 patients were tested for presence of P. jirovecii using nested polymerase chain reaction (PCR) targeting the mtLSU rRNA gene, as well as immunofluorescence microscopy. Multilocus sequence typing involving analysis of three loci-mtLSU rRNA, CYB, and SOD-was used for genotyping analysis. P. jirovecii DNA was detected in 17 (16.2%) patients. Amplification of the SOD locus was successful only in five cases (29.4% of the positive patients), while mtLSU rRNA and CYB were genotyped in all positive samples. Therefore, combined genotypes were identified based only on mtLSU rRNA and CYB loci. Eight different genotypes were identified, with Pj 1 and Pj 2 being the most prevalent (29.4% of patients each). There was no statistical correlation between these genotypes and demographic or clinical data; however, we found that infection with mutant CYB strains occurred only in patients diagnosed with lung cancer. Of the potential predictors examined, only immunosuppressive treatment was significantly associated with colonization. In conclusion, patients with various respiratory diseases, especially when immunosuppressed, are at risk of Pneumocystis colonization.

Differences Between Overlap Syndrome and Severe Sleep Apnea Syndrome In BIA/ BIvA, Adiponectin Serum Levels and in Pro- Atherogenic Indices

Introduction: The aim of the study was a comparison of body composition, adiponectin serum levels, and pro-atherogenic indices in overlap syndrome and severe sleep apnea syndrome. Methods: 33 patients with overlap syndrome (severe OSAS and COPD), 80 patients with severe OSAS and 50 persons from control group were examined. All subjects underwent polygraphy and bioelectrical impedance analysis of body composition. The adiponectin serum levels were measured using a ELISA kit. Results: To the major findings belong lower phase angle (p<0.001) and lower muscle mass percentage (p=0.005) in overlap syndrome than in OSAS patients. We showed that overlap patients had lower oxygen saturation and higher BMI and fat mass percentage than OSAS. C-reactive protein increased from control group to overlap syndrome . FEV1% correlated positive with phase angle (p<0.001) and MM% (p<0.001). Conclusions: The study showed differences between these two related syndromes, especially in body composition, oxygen saturation and in proinflammatory indices, but we didn’t observe differences in adiponectin serum levels.