Polish Cystic Fibrosis Patients' Health-Related Quality of Life and Its Influencing Factors: A Cross-Sectional, Single-Centre Study.

Cystic fibrosis (CF) is a disease characterized by long-term and troublesome symptoms that affect the patient's life. This study aimed to assess and compare the health-related quality of life (HRQoL) of Polish CF patients and identify factors influencing it. The study group consisted of 79 patients (6 to 42 years old), who filled in an age-appropriate Cystic Fibrosis Questionnaire-Revised. Medical data were collected from each patient's medical records. The domains with the highest HRQoL median were eating problems (88.89), digestive symptoms (77.78) and physical functioning (75.00). The lowest-rated domain was social functioning (61.90). Age negatively correlated with eight domains, and most strongly with treatment burden (rho = -0.474). Physical functioning positively correlated with all spirometry parameters, and most strongly with FEV1% (rho = 0.588). Treatment burden, body image and respiratory symptoms were positively correlated with all spirometry parameters except PEF%. Present exacerbations reduced scores in almost all domains, and in the MANCOVA model they were a significant factor differentiating patients' HRQoL. The univariate analysis of MANCOVA showed the significant effects of both health condition (F = 8.32, p = 0.005) and the COVID-19 pandemic (F = 5.89, p = 0.018) on social functioning domain, and of the place of residence on body image (F = 5.60, p = 0.21). A decreasing HRQoL with increasing age and during exacerbations indicates that it is important to focus on these aspects of patients' lives and ensure they received the necessary support from their healthcare providers.

Calcitonin Gene-Related Peptide Level in Cystic Fibrosis Patients.

Calcitonin gene-related peptide (CGRP) has long been implicated in both the physiology and pathophysiology of the respiratory tract. The objective of our study was to determine the serum concentration of alpha CGRP (αCGRP) in cystic fibrosis (CF) that arises from mutations in the gene responsible for encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Currently, there are not many data in the literature about the role of CGRP in CF. The serum level of αCGRP was estimated using the enzyme-linked immunosorbent assay among 64 patients with CF and 31 healthy controls. The αCGRP concentration in the CF group was 62.51 ± 15.45 pg/mL, while in the control group it was 47.43 ± 8.06 pg/mL (p < 0.001). We also compared the level of αCGRP in CF patients according to the type of CFTR mutation. Homozygotes for ΔF508 had higher αCGRP levels than heterozygotes (67.9 ± 10.2 vs. 54.5 ± 18.3 pg/mL, p < 0.01). The level of this neuropeptide was statistically higher in patients with severe disease than in those with mild CF (p = 0.003) when patients were divided into three groups by spirometry results. αCGRP concentration was not correlated with age, sex, clinical parameters, and pulmonary function test results in the study participants. The results of our study suggest a significant increase in the concentration of αCGRP in the serum of patients with CF compared to the control group. This observation opens interesting possibilities for understanding the role of αCGRP in the context of CF pathophysiology.

Changes of androgen and corticosterone metabolites excretion and conversion in cystic fibrosis.

Cystic fibrosis (CF) is a life-threatening inherited disease related to a mutation in the CFTR gene, that leads to serious health complications such as chronic pulmonary infections, pancreatic insufficiency, dysfunction of the sweat glands and reproductive system. For the first time, we have described the profile of corticosterone and androgen metabolites in urine, as well as the activity of enzymes involved in steroid genesis and metabolism in people with CF, using gas chromatography/mass spectrometry. A significant reduction in the excretion of most of the measured metabolites in CF was found. These differences were observed in the group of progestagen metabolites, as well as among metabolites of corticosterone and androgens. We revealed higher activities of 17ß-hydroxysteroid dehydrogenase and 17,20-lyase in the Δ4 pathway compared with controls, what can promote the androgen synthesis through the backdoor androgen pathway. We have also found the increased conversion activity of 11-oxyganated steroids by 5a-reductase in backdoor pathway. Levels of the most potent and vital androgens (testosterone and dihydrotestosterone) are comparable in both groups. However, the excretion of dehydroepiandrosterone was lower in CF. Decreased cholesterol lipoprotein levels may contribute to limited intracellular cholesterol supply and reduced adrenal steroidogenesis in CF individuals. Changes in the activity of some steroidogenesis enzymes may suggest the presence of some peripheral adaptive mechanisms in CF to maintain androgen balance in the body despite the limited sufficiency of secretion by the adrenal cortex.

Childhood asthma treatment based on indirect hyperresponsiveness test: Randomized controlled trial.

PURPOSE: The purpose of this study was to assess the usefulness of indirect airway hyperresponsiveness (AHR) test using hypertonic saline in determining the dose of inhaled corticosteroids (ICS) to maintain asthma control in children. METHODS: A group of 104 patients (7-15 years) with mild-moderate atopic asthma were monitored for their asthma control and treatment for 1 year. Patients were randomly assigned to a symptom-only monitored group and a group with therapy changes based on the symptoms and severity of AHR. Spirometry, exhaled nitric oxide, and blood eosinophils (BEos) were assessed on enrollment and every 3 months thereafter. RESULTS: During the study period, the number of mild exacerbations was lower in the AHR group (44 vs. 85; the absolute rate per patient 0.83 vs. 1.67; relative rate 0.49, 95% confidence interval: 0.346-0.717 (p < 0.001)]. Mean changes from baseline in clinical (except asthma control test), inflammatory, and lung function parameters were similar between groups. Baseline BEos correlated with AHR and was a risk factor for recurrent exacerbation in all patients. There was no significant difference in the final ICS dose between AHR and symptoms group: 287 (SD 255) vs. 243 (158) p = 0.092. CONCLUSIONS: Adding an indirect AHR test to clinical monitoring of childhood asthma reduced the number of mild exacerbations, with similar current clinical control and final ICS dose as in the symptom-monitored group. The hypertonic saline test appears to be a simple, cheap, and safe tool for monitoring the treatment of mild-to-moderate asthma in children.

Biomarkers of nitrosative stress in exhaled breath condensate and serum among patients with cystic fibrosis.

PURPOSE: The measurement of biomarkers in exhaled breath condensate (EBC) offers a non-invasive way to assess airway disease and can be easily done in a clinical setting among patients with cystic fibrosis (CF). The role of oxidative and nitrosative stress in the complex pathophysiology of CF is widely accepted and biomarkers of oxidative and nitrosative stress can be measured in the serum and EBC. To our knowledge, this is the first study to assess markers of nitrosative stress in EBC and serum, collected simultaneously from the CF patients. PATIENTS AND METHODS: Paired EBC and serum samples were collected from 36 stable patients with CF and 14 healthy controls. Markers of nitrosative stress ‒ 3-nitrotyrosine and nitrate/nitrite were measured in the EBC and serum using an enzyme-linked immunosorbent assay. RESULTS: We found no differences in 3-nitrotyrosine and nitrate/nitrite in the EBC of patients with CF as compared to healthy controls (125.37 â€‹± â€‹3.29 vs. 126.24 â€‹± â€‹2.21 â€‹nmol/L, p â€‹= â€‹0.218; 12.66 â€‹± â€‹7.23 vs. 8.79 â€‹± â€‹4.83 â€‹µmol/L, p â€‹= â€‹0.133, respectively). Furthermore, 3-nitrotyrosine and nitrate/nitrite were significantly higher in the serum of patients with CF as compared to the healthy controls (0.13 â€‹± â€‹0.02 vs. 0.11 â€‹± â€‹0.01 â€‹nmol/mg protein, p â€‹= â€‹0.003; 70.78 â€‹± â€‹22.55 vs. 53.08 â€‹± â€‹8.5 â€‹µmol/L, p â€‹= â€‹0.009, respectively). No correlations were found between the markers determined in the EBC and serum. CONCLUSIONS: The results of the EBC nitrosative stress biomarkers should be interpreted with caution, especially in patients with stable disease, as the EBC values may be independent on levels of circulating markers that are elevated in the serum of patients with stable CF.

Serum Appetite-Regulating Hormone Levels in Cystic Fibrosis Patients: Influence of the Disease Severity and the Type of Bacterial Infection-A Pilot Study.

Cystic fibrosis (CF) belongs to the most common inherited diseases. The severity of the disease and chronic bacterial infections are associated with a lower body index, undernutrition, higher number of pulmonary exacerbations, more hospital admissions, and increased mortality. The aim of our study was to determine the impact of the severity of the disease and the type of bacterial infection in 38 CF patients on the serum level of appetite-regulating hormones including leptin, ghrelin, neuropeptide Y, agouti-signaling protein, proopiomelanocortin, kisspeptin, putative protein Y, and α-melanocyte-stimulating hormone. The patients were divided according to the severity of the disease according to spirometry and the type of chronic bacterial infection. We found that leptin level was significantly higher in patients with severe CF than in patients with mild disease (20.02 ± 8.09 vs. 12.38 ± 6.03 ng/mL, p = 0.028). Furthermore, leptin level was elevated in patients with chronic infection with Pseudomonas aeruginosa compared to uninfected participants (15.74 ± 7.02 vs. 9.28 ± 1.72 ng/mL, p = 0.043). The severity of the disease and the type of bacterial infection did not affect the levels of other appetite-regulating hormones. Moreover, we found a positive correlation between pro-inflammatory interleukin-6 and leptin level (p = 0.0426, R = 0.333). Taken together, our results indicate that both the severity of the disease and the type of bacterial infection are associated with elevated leptin levels in CF patients. Future CF treatment strategies should consider possible disturbances in the hormones that regulate appetite and the factors that influence their levels.

Mental Health of Cystic Fibrosis Patients and the COVID-19 Pandemic in Poland: A Single-Center Comparative Study.

Research shows that people with cystic fibrosis are more prone to suffer from psychological problems than healthy people; thus, the outbreak of the COVID-19 pandemic in Poland could have had an impact on their mental health. To assess this impact, we examined the mental health of patients before and during the pandemic. Survey participants were asked to fill in questionnaires that consisted of Beck Depression Inventory (BDI), 12-Item General Health Questionnaire (GHQ-12) and Cystic Fibrosis Questionnaire-Revised (CFQ-R; for the purpose of the study, an emotional functioning domain was used) during their hospital visits. A total of 81 patients took part in the study: 39 before the COVID-19 pandemic (BP) and 42 during the COVID-19 pandemic (DP). Patients' medians were lower for the BDI, GHQ-12 and higher for the emotional domain of CFQ-R during the pandemic (3, 6, 75 vs. 4, 10, 73.33). Fewer patients felt that their mental health had deteriorated during the pandemic (Δχ2 = 7.723; p = 0.005), and GHQ-12 scores were lower in the DP group (Z = -3.044; p = 0.002). No significant differences were found between groups in terms of experiencing depressive symptoms (Δχ2 = 1.036; p = 0.309). It was found that patients with cystic fibrosis from our study group not only maintained but also improved their mental health state during the COVID-19 pandemic.

Alteration in glucocorticoids secretion and metabolism in patients affected by cystic fibrosis.

Cystic fibrosis (CF) is an inherited syndrome associated with a mutation in a cystic fibrosis transmembrane conductance regulator gene, composed of exocrine gland dysfunction involving multiple systems that may result in chronic respiratory infections, pancreatic enzyme deficiency, and developmental disorders. Our study describes for the first time the urinary profile of glucocorticoid metabolites and the activity of the enzymes involved in the development and metabolism of cortisol in patients with CF, using a gas chromatography/mass spectrometry method. Data were obtained from 25 affected patients and 70 sex- and age- matched healthy volunteers. We have shown a general decrease in the activity of enzymes involved in the peripheral metabolism of cortisol, such as 11ß-hydroxysteroid dehydrogenase type 2, 5α- and 5ß-reductases. In contrast, the activity of 11ß-hydroxysteroid dehydrogenase type 1, the enzyme that converts cortisone to cortisol, increased. Furthermore, our study found a significant decrease in glucocorticoid excretion in patients with CF. This may suggest adrenal insufficiency or dysregulation of the HPA axis and the development of peripheral mechanisms to counteract cortisol degradation in the case of reduced synthesis of glucocorticoids by the adrenal glands. Furthermore, the activity of 5α-reductase seems to be enhanced only through the backdoor pathway, especially when we taking into consideration 11ß-hydroxyandrosterone/11ß-hydroxyetiocholanolone ratio which has been shown to be the best differential marker for enzyme activity. CF impairs nutritional effects and energetic balance in patients; thus, our findings suggest the existence of adaptive mechanisms due to limited secretion of adrenal steroids and subsequent diminished amounts of their metabolites in urine. On the other hand, local control of cortisol availability is maintained by enhanced 11ßHSD1 activity and its recovery from cortisone in organs and tissues which need this. Steroid hormone dysregulation might be another important factor in the course of CF that should be taken into account when planning an effective and comprehensive therapy.

Serum kisspeptin and proopiomelanocortin in cystic fibrosis: a single study.

The determination of hormonal biomarkers is of increasing interest in many diseases, including cystic fibrosis (CF). Hormones that have not been estimated and described so far in CF include kisspeptin (KISS) and proopiomelanocortin (POMC), which are involved in the regulation of many processes, including appetite and fertility. Therefore, the aim of our study was to estimate the level of KISS and POMC in sera from CF patients and to determine the correlation between these hormones and clinical parameters. For this purpose, we estimated the levels of KISS and POMC in 38 CF patients and 16 healthy participants with enzyme-linked immunosorbent assay. We found significantly reduced levels of KISS and POMC in people with CF compared to healthy subjects (1.76 ± 0.46 vs. 2.27 ± 0.56 ng/mL, p < 0.05 and 6.25 ± 4.36 vs. 14.74 ± 6.24 ng/mL, p < 0.001, respectively). Furthermore, the level of both hormones was negatively correlated with age. The hormones studied did not correlate with the results of spirometry and each other. Thus, decreased KISS and POMC levels may be associated with lower body weight and delayed puberty in patients with CF.

Serum levels of hormones regulating appetite in patients with cystic fibrosis - a single-center, cross-sectional study.

Cystic fibrosis (CF), which is the most common inherited genetically determined disease caused by a mutation in the gene for the CF transmembrane conductance regulator protein. Pulmonary failure is the leading cause of death in this population, while the dysregulation of endocrine system creates significant disorders, including malnutrition, underweight, and CF-related diabetes. Therefore, the objective of our study was to determine the following hormones in the serum of patients with CF: ghrelin, putative peptide YY (PYY), Agouti-signaling protein (ASP), and alpha-melanocyte-stimulating hormone (α-MSH). To our knowledge, serum levels of PYY, ASP, and α-MSH have not yet been assessed in CF. For this purpose, we measured hormone levels using enzyme-linked immunosorbent assays in 38 patients from the local CF care center, as well as 16 sex- and age-matched healthy controls. Moreover, we estimated the correlations between the tested hormones and the parameters of the patients' clinical status. In this study, we found sinificantly reduced serum levels of ghrelin and ASP in patients with CF (p<0.01). There was no difference in PYY and α-MSH levels between participants with CF and healthy subjects. Furthermore, there was no difference in hormone levels between females and males with CF. The type of gene mutation (homozygous or heterozygous for ΔF508) had no effect on hormone levels. Ghrelin was negatively correlated with age, body mass index, and C-reactive protein. PYY was negatively associated with the age of the patients. Hormone dysregulation in CF may contribute to decreased appetite, as well as many other disturbed processes. Therefore, ghrelin appears to play a key role in the regulation of energy management of CF. Future multicenter and multidisciplinary studies should focus on an unequivocal understanding of the role of these hormones in CF.

Serum leptin and neuropeptide Y in patients with cystic fibrosis-A single center study.

Along with the significant elongation in the average life expectancy of patients with cystic fibrosis (CF), there are still significant discrepancies in the height, weight, and body mass index (BMI) of patients compared to controls without CF. The correlation between hormones that regulate appetite and body fat mass may be an additional factor in weight loss or poor weight gain in CF patients. Our objective was to estimate serum concentrations of leptin and neuropeptide Y in patients with CF as well as to assess correlations between studied hormones and the clinical parameters of CF. Leptin and neuropeptide Y serum concentrations after an overnight fast were measured using an enzyme-linked immunosorbent assay. All study participants had anthropometric tests and spirometry. In addition, fasting serum lipid profile was also analyzed. Fasting leptin levels in CF were significantly higher in patients with CF patients (13.9 ± 6.9 vs. 6.5 ± 2.6 ng/mL, p < 0.001) compared to controls. There were no differences in leptin concentration between female and male CF participants (15.7 ± 7.8 vs. 12.2 ± 5.6 ng/mL, p = 0.13). Leptin was correlated with age (R = 0.64, p < 0.001), BMI (R = 0.65, p < 0.001), spirometry results (R = -0.49, p < 0.01), and body fat (R = 0.5, p < 0.05). There were no differences in neuropeptide Y concentration between participants with CF and controls as well as neuropeptide Y was not correlated with any studied parameters. The results of our study suggest that weight loss may be associated with a decreased level of leptin, while reduced pulmonary function in CF may be related to an elevated level of leptin.

The Role of Oxidative Stress in Atopic Dermatitis and Chronic Urticaria.

Atopic dermatitis (AD) and chronic urticaria (CU) are common skin diseases with an increasing prevalence and pathogenesis that are not fully understood. Emerging evidence suggests that oxidative stress plays a role in AD and CU. The aim of the single-center cross-sectional study was to compare markers of oxidative stress in 21 patients with AD, and 19 CU patients. The products of protein oxidation, total antioxidant capacity (TAC), and markers of lipid peroxidation were estimated in the serum. AD patients had a higher level of advanced protein oxidation products and a lower level of thiol groups than healthy participants. However, CU patients had statistically higher levels of AOPP and 3-nitrotyrosine than healthy subjects. The level of thiol groups and serum TAC decreased significantly in patients with CU. There was no difference in serum concentration of lipid peroxidation products, Amadori products, ratio of reduced to oxidized glutathione, and ability of albumin to binding cobalt between AD or CU patients compared to healthy subjects. We found a moderate positive significant correlation between AOPP and age in patients with AD. In patients with CU, TAC was negatively correlated with age. These results may shed light on the etiopathogenesis of AD or CU, and confirm an oxidative burden in these patients. Furthermore, our study could be useful in developing new therapeutic methods that include using antioxidants in dermatological diseases.

Fractional Exhaled Nitric Oxide in Teenagers and Adults with Atopic Dermatitis.

Fractional exhaled nitric oxide (FeNO) is a non-invasive biomarker of eosinophilic airway inflammation and therapeutic response to corticosteroid treatment of respiratory diseases. Atopic dermatitis (AD), one of the most common allergic conditions of the skin, is a factor influencing the increase of FeNO. The main aim of this study was to determine differences between levels of FeNO in patients with AD and healthy controls as measured by an electrochemical analyzer. In total, 54 teenagers and adults with AD were recruited and compared with 34 healthy volunteers. The measurements of FeNO were taken using the Hyp'Air FeNO in participants. FeNO was statistically significantly higher in patients with AD than in healthy controls (60.5 ± 35.1 vs. 14.8 ± 5.1 ppb, p < 0.001). We found a strong positive significant correlation between FeNO and the number of positive skin prick tests among AD patients (R = 0.754, p < 0.001). There was no correlation between FeNO and duration of disease as well as SCORAD index among patients. Moreover, we also found no FeNO difference between the mild and moderate forms of AD. The presence of AD and the increasing number of positive skin prick tests increase FeNO, so the results of this measurement should be interpreted with caution in patients with respiratory diseases suffering from AD.

Links between Disease Severity, Bacterial Infections and Oxidative Stress in Cystic Fibrosis.

Cystic fibrosis (CF) is one of the most common, yet fatal genetic diseases in Caucasians. The presence of a defective CF transmembrane conductance regulator and the massive neutrophils influx into the airways contribute to an imbalance in epithelial cell processes and extracellular fluids and lead to excessive production of reactive oxygen species and intensification of oxidative stress. The study included 16 controls and 42 participants with CF aged 10 to 38. The products of protein oxidation, total antioxidant capacity (TAC) and markers of lipid peroxidation were estimated in the serum of the subjects. Furthermore, we compared the level of oxidative stress in patients with CF according to the severity of disease and type of bacterial infection. Thiol groups and serum TAC decreased significantly in patients with CF (p < 0.05). Elevated levels of 3-nitrotyrosine, malondialdehyde and 8-isoprostane were observed in CF subjects (p < 0.05). Furthermore, as the severity of the disease increased, there was a decrease in the thiol groups and TAC levels, as well as an increase in the concentration of 3-nitrotyrosine and 8-isoprostane. CF participants infected with Pseudomonas aeruginosa had elevated 3-nitrotyrosine concentration levels (p < 0.05), while those infected with Staphylococcus aureus noted a decrease in thiol groups (p < 0.05). Elevated levels of oxidative stress markers were found in the serum of CF patients. Furthermore, oxidative stress progressively increased over the years and along with the severity of the disease. The presence of bacterial infection with P. aeruginosa or S. aureus had a slight effect on oxidative stress, while co-infection by two species did not affect the level of oxidative stress.

Renal Function in Patients with Cystic Fibrosis: A Single-Center Study.

Cystic fibrosis (CF) is the most common incurable autosomal recessive disease affecting the Caucasian population. As the prognosis for life extension of CF patients improves, co-morbidities, including kidney disease, become more common. Identifying those at the highest risk of kidney injury is therefore extremely important. The aim of this study was to evaluate the biomarkers of renal function in 50 CF patients using the estimated glomerular filtration rate (eGFR) based on creatinine and cystatin C equation as well as serum creatinine (sCr), serum cystatin C (CysC), serum urea and urinary neutrophil gelatinase-associated lipocalin (uNGAL) concentrations. sCr, CysC, urea and uNGAL were estimated. eGFR was calculated according to the CKD-EPI formula. CysC was significantly increased, while eGFR was significantly lower in the CF group than in the controls (p < 0.001 and p < 0.01, respectively). There was no significant difference in the sCr, urea and uNGAL concentrations between patients with CF and healthy subjects. For the purpose of our analysis, in order to assess renal function in patients with CF in clinical practice, the concentration of serum CysC and eGFRCKD-EPI should be determined. Patients with CF presented with renal function impairment pictured by increased serum CysC and decreased eGFR values compared to controls. Unchanged uNGAL concentrations suggested preserved tubular function despite aminoglycoside treatment. Further prospective studies are needed to clarify whether kidney impairment observed in the course of CF progresses.

Cystic Fibrosis-Related Diabetes in Poland.

Cystic fibrosis (CF) is the most common autosomal recessive inherited monogenic disease in Caucasians. As medical technology progresses and the quality of patient care improves, the survival time of patients with CF has increased, which results in more frequent comorbidities such as cystic fibrosis-related diabetes (CFRD). CFRD is the result of abnormal glucose metabolism characterized primarily by insulin deficiency, exacerbated periodically by insulin resistance. The aim of our study was to analyze the epidemiology of patients with CFRD in Poland on the basis of data collected from six CF treatment centers. Analyses were performed on 1157 CF patients who were treated at one of the six CF care centers. CFRD was diagnosed according to standard criteria. All data including demographics, types of CFTR mutations, CFRD duration, and microorganisms in the sputum were obtained from the patients' medical history. Our study indicates that the prevalence of CFRD in Poland is 12.9%. CFRD was most often diagnosed between the ages of 11 and 20 (60% of patients), while 23% of patients were diagnosed between 21 and 30 years of age. Furthermore, we observed that approximately 3-5% of patients under the age of 10 had CFRD. We found out that the type of mutation did not affect the frequency of CFRD development. Factors that increased the risk of developing CFRD include underweight and chronic Pseudomonas aeruginosa infection. Due to the extended lifespan of CF patients, the number of CFRD patients is currently increasing. We believe that the results of our study may complement information from other studies or may be useful in planning health policy in Poland.

Comparison of fractional exhaled nitric oxide in asthmatics with and without allergic rhinitis.

PURPOSE OF THE STUDY: The aim of this study was to measure the concentration of FeNO in asthmatics with and without allergic rhinitis (AR) and to determine usefulness of the test in the assessment of asthma control in the Polish population. The next objective of this study was to estimate the cut-off point of FeNO which might be a good indicator of uncontrolled asthma. MATERIALS AND METHODS: The measurements were taken using the Hyp'Air FeNO in 303 adult patients with asthma, AR, comorbid AR and asthma, and non-diseased volunteers. RESULTS: FeNO level in healthy adults was similar to the FeNO concentration in AR as well as controlled asthmatic patients without and with AR. Patients with partly controlled and uncontrolled asthma with and without AR had higher FeNO (>60 ppb) levels when compared to adults with controlled disease. The optimal cut-off point of FeNO > 46 ppb and FeNO > 33 ppb was estimated for identification of uncontrolled asthmatics without and with AR, respectively. CONCLUSION: In conclusion, we found a significant correlation between the FeNO concentration and the level of asthma symptom control in asthmatic patients with and without AR.

Polyvalent Mechanical Bacterial Lysate Administration Improves the Clinical Course of Grass Pollen-Induced Allergic Rhinitis in Children: A Randomized Controlled Trial.

BACKGROUND: Recent studies highlight the immunoregulatory potential of bacterial lysates, indicating their potential use in the prevention and treatment of allergic diseases. OBJECTIVE: To investigate the clinical efficacy of polyvalent mechanical bacterial lysates (PMBLs) in children with grass pollen-induced allergic rhinitis. METHODS: Seventy children with seasonal allergic rhinitis were enrolled to this study and were randomly assigned to the PMBL and placebo groups. Severity of seasonal allergic rhinitis symptoms was assessed by the total nasal symptom score, total ocular symptom score, and visual analogue scale. During 3 visits, peak nasal inspiratory flow was measured, and nasal smears for the presence of eosinophils and nasal lavage fluids for the presence of allergen-specific IgE against timothy grass pollen allergens were sampled. RESULTS: A statistically significant decrease in total nasal symptom score (P = .001), total ocular symptom score (P = .04), and visual analogue scale score for nasal and eye symptoms (P < .001 and P < .001, respectively) and an increase in peak nasal inspiratory flow (P = .04) were observed in the PMBL group versus the placebo group. During the grass pollen season, an increase and then a decrease in the number of eosinophils in nasal smears was observed in both groups; however, the number of eosinophils was significantly lower in the PMBL group versus the placebo group. No significant changes in allergen-specific IgE concentrations were observed in the PMBL group, whereas in the placebo group a statistically significant increase in allergen-specific IgE concentration was observed. CONCLUSIONS: Sublingual administration of PMBLs during the grass pollen season offers significant efficacy in alleviating seasonal allergic rhinitis symptoms in children sensitized to grass pollen allergens. PMBLs probably affect mucosal immunity, weakening the response of TH2 cells.

Safety and efficacy of lenabasum in a phase 2 randomized, placebo-controlled trial in adults with cystic fibrosis.

BACKGROUND: Few therapies specifically address the chronic airway inflammation in cystic fibrosis (CF) that contributes to progressive destruction of lung tissue and loss of lung function. Lenabasum is a cannabinoid type 2 receptor (CB2) agonist that resolves inflammation in a number of in vitro and in vivo models. METHODS: A Phase 2 double-blind, randomized, placebo-controlled study assessed the safety and tolerability of lenabasum in adults with CF. Subjects with FEV1% (ppFEV1) ≥40% predicted were randomized to lenabasum 1 or 5 mg or placebo once daily (QD) (Weeks 1-4), then 20 mg QD, 20 mg twice daily (BID) or placebo (Weeks 5-12), with follow-up at Week 16. Pulmonary exacerbations (PEx) were recorded and biomarkers of blood and lung inflammation were measured. RESULTS: Of 89 subjects randomized, 51 lenabasum and 23 placebo-only subjects completed the study. No deaths or serious or severe adverse events (AE) were considered related to lenabasum. Most AEs were mild/moderate, and the most common were PEx, hemoptysis, dry mouth, and upper respiratory infection. Three lenabasum and one placebo-only subjects discontinued the study for a treatment related AE. New PEx were treated with intravenous antibiotics in 4.0% of lenabasum-treated vs. 11.4% of placebo-treated subjects, during Weeks 1-4 and 5.2% compared to 13.0% during Weeks 5-12 (p<0.2). No significant differences in ppFEV1 were observed between treatment groups. Sputum neutrophils, eosinophils, and neutrophil elastase were numerically reduced, and significant (p<0.05) reductions in IL-8 and immunoglobulin G levels occurred with lenabasum. CONCLUSIONS: The safety findings of lenabasum, coupled with biomarker data, support further testing in a larger study with a longer duration.

Managing Cystic Fibrosis in Polish Healthcare.

The quality and length of life of patients with cystic fibrosis (CF) are determined by a number of factors including the quality of healthcare received by patients, as well as access to drug programs dedicated to this particular disease. The purpose of this paper is to present an overview of changes in the average life expectancy and mortality rate of the CF population in Poland between 2000 and 2018. Furthermore, we would like to evaluate access to healthcare services, including the drug program, guaranteed by public healthcare system, and funded by National Health Fund (NHF). The average life expectancy of patients with CF increased in the period in question from ca. 14.5 ± 7.6-24.5 ± 8.9 years (mean ± SD, p = 0.0001). We have observed a drop in the number of deaths in paediatric age during that period. Despite the increase in life expectancy, the use of health resources in patients with CF, especially the drug program, is dramatically low. Considering the fact that in Poland there was no active countrywide CF registry, now it is possible to estimate the frequency of use of CF healthcare services in various provinces exclusively on the basis of database maintained by the Polish NHF.