Safety and efficacy of the epithelial sodium channel blocker idrevloride in people with primary ciliary dyskinesia (CLEAN-PCD): a multinational, phase 2, randomised, double-blind, placebo-controlled crossover trial.

BACKGROUND: Mucociliary clearance is dysfunctional in people with primary ciliary dyskinesia, resulting in the accumulation of dehydrated mucus in the airways that is difficult to clear. We undertook a study to assess the benefit on lung function of treatment with a nebulised epithelial sodium channel (ENaC) blocker, idrevloride, with or without hypertonic saline, in people with primary ciliary dyskinesia. METHODS: The CLEAN-PCD trial was a phase 2, randomised, double-blind, placebo-controlled crossover trial conducted at 32 tertiary adult and paediatric care centres and university hospitals in Canada, Denmark, Germany, Italy, the Netherlands, Poland, the UK, and the USA. People with a confirmed diagnosis of primary ciliary dyskinesia, aged 12 years or older, with a percentage of predicted FEV1 (ppFEV1) in the range of 40% to <90%, were randomly assigned in a 2:2:1:1 ratio (block size=6), stratified by ppFEV1 at screening, to one of four sequences: (1) idrevloride in hypertonic saline in treatment period 1 then hypertonic saline in treatment period 2; (2) hypertonic saline in treatment period 1 then idrevloride in hypertonic saline in treatment period 2; (3) idrevloride in treatment period 1 then placebo in treatment period 2; and (4) placebo in treatment period 1 then idrevloride in treatment period 2. The idrevloride dose was 85 µg and hypertonic saline was 4·2% NaCl. 3 mL of each study treatment was nebulised twice daily for 28 days in treatment periods 1 and 2; the two 28-day treatment periods were separated by a 28-day washout period. The primary endpoint was absolute change from baseline in ppFEV1 after 28 days. Safety assessments and reports of adverse events were made at clinic visits during each treatment period and by a follow-up telephone call 28 days after the last dose of study drug. Additionally, adverse events could be reported at a follow-up telephone call 3 days after the start of dosing and as they arose. Participants who received at least one dose of study drug were included in the safety analyses (safety set), and those who also had spirometry data were included in the efficacy analyses (full analysis set). The completed study is registered (EudraCT 2015-004917-26; ClinicalTrials.govNCT02871778). FINDINGS: Between Sep 14, 2016, and May 31, 2018, 216 patients were screened and 123 were randomly assigned to one of four crossover sequences. Across the two treatment periods, treatment with idrevloride in hypertonic saline was initiated in 80 patients and completed in 78 patients (all 78 had data available and were included in the analysis); hypertonic saline initiated in 81 patients and completed in 76 patients (75 had data available and were included in the analysis); idrevloride initiated in 37 patients and completed in 35 patients (34 had data available and were included in the analysis); and placebo initiated in 36 patients and completed in 34 patients (all 34 had data available and were included in the analysis). Greater absolute increases in ppFEV1 from baseline to 28 days of treatment were seen with idrevloride in hypertonic saline (least-squares mean absolute change from baseline 1·0 percentage points, 95% CI -0·4 to 2·4) than with hypertonic saline alone (least-squares mean absolute change from baseline of -0·5 percentage points, -2·0 to 0·9; difference 1·5 percentage points, 95% CI <0·1 to 3·0; p=0·044). There was no significant difference in ppFEV1 for the parallel comparison of idrevloride in hypertonic saline compared with placebo or the crossover comparison of idrevloride with placebo. Adverse events were similar across treatments (57 to 65% of patients). Cough occurred in a greater proportion of participants during treatments that contained idrevloride or hypertonic saline compared with placebo, and oropharyngeal pain occurred in a greater proportion of participants during idrevloride treatments than during treatment with hypertonic saline alone or placebo, whereas chest discomfort was more common during treatments that included hypertonic saline. INTERPRETATION: In this phase 2 crossover study, idrevloride in hypertonic saline was safe and associated with improved lung function over a 28-day period in people with primary ciliary dyskinesia compared with hypertonic saline alone. Larger, longer clinical studies are warranted to explore the potential benefits of idrevloride in combination with hypertonic saline in people with primary ciliary dyskinesia. FUNDING: Parion Sciences, under agreement with Vertex Pharmaceuticals.

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.

The Effects of Gabapentin on Post-Operative Pain and Anxiety, Morphine Consumption and Patient Satisfaction in Paediatric Patients Following the Ravitch Procedure-A Randomised, Double-Blind, Placebo-Controlled, Phase 4 Trial.

The aim of the study was to investigate whether the use of pre- and postoperative gabapentin can decrease postoperative pain, morphine consumption, anxiety and side effects, as well as improve patient satisfaction. A total of 56 patients, 9−17 years of age, undergoing a modified Ravitch procedure, were randomised (allocation ratio 1:1) to receive multiple perioperative doses of gabapentin (preoperatively 15 mg/kg, postoperatively 7.5 mg/kg, two times per day for three days) or a placebo. All the patients received intravenous infusion of morphine, paracetamol and non-steroidal anti-inflammatory drugs. Metamizole was given as a "rescue drug". The observation period included the day of surgery and three postoperative days. The primary outcomes were postoperative pain intensity (at rest, during deep breathing and coughing). Additional outcomes included the consumption of morphine, the total number of doses of metamizole, anxiety, postoperative side effects and patient satisfaction. Median average and maximal pain scores (on the day of surgery and on the second postoperative day) were significantly lower only in the gabapentin group at rest (p < 0.05). Compared to the placebo group, gabapentin treatment reduced the demand for morphine on the first postoperative day (median 0.016 vs. 0.019 mg/kg/h; p = 0.03) and the total number of metamizole doses (median 1 vs. 2 p = 0.04). Patient satisfaction was significantly greater in the gabapentin group (median 10 vs. 9; p = 0.018). Anxiety and postoperative side effects were similar in both groups (p > 0.05). Pre- and postoperative gabapentin administration as part of a multimodal analgesic regimen may decrease postoperative pain, opioid consumption and demand for a "rescue drug", as well as improve patient satisfaction.

Oral Hygiene and Periodontal Treatment Needs in Adult Patients with Cystic Fibrosis (CF).

Cystic Fibrosis (CF) is an autosomal multisystem recessive genetic disease. Patients with Cystic Fibrosis, oral bacteria related to dental and periodontal diseases that can also inhabit the lungs, increases the risk for systemic complications. Our study aimed at assessing oral hygiene status of cystic fibrosis adult patients. The study was conducted on 40 patients diagnosed with CF and 40 healthy participants. The following indices were included: Simplified Oral Hygiene (OHI-S), Approximal Plaque Index (API), Community Periodontal Index of Treatment Needs (CPITN), and a questionnaire. Obtained results proved that the API was 44.63% in the study group, indicating sufficient hygiene, and 37% in the control group, indicating quite good hygiene. Significantly higher OHI-S was found in the study group. It was found based on the analysis of treatment needs that home care and professional instructions on proper oral hygiene were more often needed in the control group compared to CF patients. In conclusion, the obtained API and OHI-S values in adult CF patients were indicative of satisfactory oral hygiene. Periodontal treatment needs assessed based on the CPITN index in patients with CF indicated the need for professional preventive treatments. An interdisciplinary dental care to support oral health could be recommendable in individuals with chronic respiratory diseases such as Cystic Fibrosis.

Risk Factors and Protective Factors against Ventilator-Associated Pneumonia-A Single-Center Mixed Prospective and Retrospective Cohort Study.

Introduction: Understanding the factors associated with the development of ventilator-associated pneumonia (VAP) in critically ill patients in the intensive care unit (ICU) will allow for better prevention and control of VAP. The aim of the study was to evaluate the incidence of VAP, as well as to determine risk factors and protective factors against VAP. Design: Mixed prospective and retrospective cohort study. Methods: The cohort involved 371 critically ill patients who received standard interventions to prevent VAP. Additionally, patients in the prospective cohort were provided with continuous automatic pressure control in tapered cuffs of endotracheal or tracheostomy tubes and continuous automatic subglottic secretion suction. Logistic regression was used to assess factors affecting VAP. Results: 52 (14%) patients developed VAP, and the incidence density of VAP per 1000 ventilator days was 9.7. The median days to onset of VAP was 7 [4; 13]. Early and late onset VAP was 6.2% and 7.8%, respectively. According to multivariable logistic regression analysis, tracheotomy (OR = 1.6; CI 95%: 1.1 to 2.31), multidrug-resistant bacteria isolated in the culture of lower respiratory secretions (OR = 2.73; Cl 95%: 1.83 to 4.07) and ICU length of stay >5 days (OR = 3.32; Cl 95%: 1.53 to 7.19) were positively correlated with VAP, while continuous control of cuff pressure and subglottic secretion suction used together were negatively correlated with VAP (OR = 0.61; Cl 95%: 0.43 to 0.87). Conclusions: Tracheotomy, multidrug-resistant bacteria, and ICU length of stay >5 days were independent risk factors of VAP, whereas continuous control of cuff pressure and subglottic secretion suction used together were protective factors against VAP.

Lung function from school age to adulthood in primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) presents with symptoms early in life and the disease course may be progressive, but longitudinal data on lung function are scarce. This multinational cohort study describes lung function trajectories in children, adolescents and young adults with PCD. We analysed data from 486 patients with repeated lung function measurements obtained between the age of 6 and 24 years from the International PCD Cohort and calculated z-scores for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio using the Global Lung Function Initiative 2012 references. We described baseline lung function and change of lung function over time and described their associations with possible determinants in mixed-effects linear regression models. Overall, FEV1, FVC and FEV1/FVC z-scores declined over time (average crude annual FEV1 decline was -0.07 z-scores), but not at the same rate for all patients. FEV1 z-scores improved over time in 21% of patients, remained stable in 40% and declined in 39%. Low body mass index was associated with poor baseline lung function and with further decline. Results differed by country and ultrastructural defect, but we found no evidence of differences by sex, calendar year of diagnosis, age at diagnosis, diagnostic certainty or laterality defect. Our study shows that on average lung function in PCD declines throughout the entire period of lung growth, from childhood to young adult age, even among patients treated in specialised centres. It is essential to develop strategies to reverse this tendency and improve prognosis.

Automatic Continuous Control of Cuff Pressure and Subglottic Secretion Suction Used Together to Prevent Pneumonia in Ventilated Patients-A Retrospective and Prospective Cohort Study.

The ventilator bundle consists of multiple methods to reduce ventilator-associated pneumonia (VAP) rates in Intensive Care Units (ICU). The aim of the study was to evaluate how the continuous automatic pressure control in tapered cuffs of endotracheal/tracheostomy tubes applied along with continuous automatic subglottic secretion suction affect the incidence of VAP. In the prospective cohort (n = 198), the standard VAP bundle was modified by continuous automatic pressure control in taper-shaped cuff of endotracheal/tracheostomy tubes and subglottic secretion suction. VAP incidence, time to VAP onset, invasive mechanical ventilation days/free days, length of ICU stay, ICU mortality, and multidrug-resistant bacteria were assessed and compared to the retrospective cohort (n = 173) with the standard bundle (intermittent cuff pressure of standard cuff, lack of subglottic secretion suction). A smaller incidence of VAP (9.6% vs. 19.1%) and early onset VAP (1.5% vs. 8.1%) was found in the prospective compared to the retrospective cohort (p < 0.01). Patients in the prospective cohort were less likely to develop VAP (RR = 0.50; 95% CI: 0.29 to 0.85) and early-onset VAP (RR = 0.19; 95% CI: 0.05 to 0.64) and had longer time to onset VAP (median 9 vs. 5 days; p = 0.03). There was no significant difference (p > 0.05) between both cohorts in terms of invasive mechanical ventilation days/free days, length of ICU stay, ICU mortality and multidrug-resistant bacteria. Modification of the bundle for prevention of VAP can reduce early-onset VAP and total incidence of VAP and delay the time of VAP occurrence.

Relationship Between Air Pollution and the Concentration of Nitric Oxide in the Exhaled Air (FeNO) in 8-9-Year-Old School Children in Krakow.

The consequences of air pollution pose one of the most serious threats to human health, and especially impact children from large agglomerations. The measurement of nitric oxide concentration in exhaled air (FeNO) is a valuable biomarker in detecting and monitoring airway inflammation. However, only a few studies have assessed the relationship between FeNO and the level of air pollution. The study aims to estimate the concentration of FeNO in the population of children aged 8-9 attending the third grade of public primary schools in Krakow, as well as to determine the relationship between FeNO concentration and dust and gaseous air pollutants. The research included 4580 children aged 8-9 years who had two FeNO measurements in the winter-autumn and spring-summer periods. The degree of air pollution was obtained from the Regional Inspectorate of Environmental Protection in Krakow. The concentration of pollutants was obtained from three measurement stations located in different parts of the city. The FeNO results were related to air pollution parameters. The study showed weak but significant relationships between FeNO and air pollution parameters. The most significant positive correlations were found for CO8h (r = 0.1491, p < 0.001), C6H6 (r = 0.1420, p < 0.001), PM10 (r = 0.1054, p < 0.001) and PM2.5 (r = 0.1112, p < 0.001). We suggest that particulate and gaseous air pollutants impact FeNO concentration in children aged 8-9 years. More research is needed to assess the impact of air pollution on FeNO concentration in children. The results of such studies could help to explain the increase in the number of allergic and respiratory diseases seen in children in recent decades.

Chronic bacterial pulmonary infections in advanced cystic fibrosis differently affect the level of sputum neutrophil elastase, IL-8 and IL-6.

Advanced cystic fibrosis (CF) lung disease is commonly characterized by a chronic Pseudomonas aeruginosa infection and destructive inflammation caused by neutrophils. However, the lack of convincing evidence from most informative biomarkers of severe lung dysfunction (SLD-CF) has hampered the formulation of a conclusive, targeted diagnosis of CF. The aim of this study was to determine whether SLD-CF is related to the high concentration of sputum inflammatory mediators and the presence of biofilm-forming bacterial strains. Forty-one patients with advanced CF lung disease were studied. The severity of pulmonary dysfunction was defined by forced expiratory volume in 1 second (FEV1) < 40%. C-reactive protein (CRP) and NLR (neutrophil-lymphocyte ratio) were examined as representative blood-based markers of inflammation. Expectorated sputum was collected and analysed for cytokines and neutrophil-derived defence proteins. Isolated sputum bacteria were identified and their biofilm-forming capacity was determined. There was no association between FEV1% and total number of sputum bacteria. However, in the high biofilm-forming group the median FEV1 was < 40%. Importantly, high density of sputum bacteria was associated with increased concentrations of neutrophil elastase and interleukin (IL)-8 and low concentrations of IL-6 and IL-10. The low concentration of sputum IL-6 is unique for CF and distinct from that observed in other chronic pulmonary inflammatory diseases. These findings strongly suggest that expectorated sputum is an informative source of pulmonary biomarkers representative for advanced CF and may replace more invasive bronchoalveolar lavage analysis to monitor the disease. We recommend to use of the following inflammatory biomarkers: blood CRP, NLR and sputum elastase, IL-6, IL-8 and IL-10.

Plastic Bronchitis-A Serious Rare Complication Affecting Children Only after Fontan Procedure?

BACKGROUND: Plastic bronchitis (PB) may occur not only in children following palliative Fontan procedure but also in those without underlying heart disease. We aim to assess the clinical course, therapeutic measures, outcome, and follow-up of PB in children with congenital heart disease (CHD) and children without cardiac problems. METHODS: This retrospective case series assessed children with PB admitted to hospital between 2015 and 2019. Parents or guardians of patients were contacted by e-mail or telephone between September 2017 and June 2019 to enquiry about recurrence of PB and strategy of treatment. The diagnosis of PB was based on the expectoration (spontaneous or during bronchoscopy) of endobronchial plugs. RESULTS: This study delineated the clinical, histological, and laboratory features of plastic bronchitis in children following Fontan procedure (Group A) and in those without heart defects (Group B, non-CHD children). The main symptoms were cough accompanied by dyspnea, and hypoxemia with a decrease in oxygen saturation, often leading to acute respiratory failure. In children with CHD, the first episode of PB occurred at a relatively young age. Although chronic, i.e., lasting more than 3 weeks, inhaled therapy was implemented in both groups of patients, the recurrences of PB were observed. The mean time to PB recurrence after the first episode in Group A was longer than that in Group B (1.47 vs. 0.265 years, p = 0.2035). There was no re-episode with recurrence of PB in 3 cases out of 10 in total in Group A (30%) and 1 case out of 4 in total in Group B (25%). While the majority of children in Group A usually developed bronchial casts on the right side, the patients in Group B (without CHD) suffered from bronchial casts located only on the left side. CONCLUSIONS: Despite many similarities, clinical, histological, and laboratory studies in the children with plastic bronchitis after Fontan's surgery and in children without heart defects suggest that there are differences in the course of the disease in patients without CHD, such as a more advanced age of the first episode of PB, the location of plastic casts on the left side, and a stronger role of inflammatory factors and mechanisms. Further research is needed to understand the pathophysiology of PB and choose the most appropriate therapy.

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.

Aerosolized lancovutide in adolescents (≥12 years) and adults with cystic fibrosis - a randomized trial.

BACKGROUND: Lancovutide activates a chloride channel (TMEM-16A) other than the cystic fibrosis (CF) transmembrane conductance regulator protein and could benefit CF patients. METHODS: In this randomized, multi-center, double-blind, placebo-controlled, parallel-group trial 161 patients ≥12 years with a confirmed diagnosis of CF were randomized to either placebo (saline) or active drug in 3 different dosing schemes of 2.5mg inhaled lancovutide (once daily, every other day or twice a week) for eight weeks. The primary endpoint was the change in the forced expiratory volume in 1 second (FEV1) percent predicted. Secondary endpoints included further lung function parameters (FEV1 (absolute), functional vital capacity percent predicted, forced expiratory flow percent predicted, pulse oximetry), quality of life assessment, pulmonary exacerbations, hospitalization due to pulmonary exacerbations, time to first pulmonary exacerbation, duration of anti-inflammatory, mucolytic or antibiotic treatment, and safety. RESULTS: There was no significant difference in the change in FEV1 percent predicted, quality of life, other lung function parameters, pulmonary exacerbations or requirement of additional treatment between groups. Overall, the inhalation of lancovutide was safe although a higher rate of adverse events, especially related to the respiratory system, occurred as compared to placebo. CONCLUSIONS: Lancovutide did not improve FEV1 percent predicted when compared to placebo (NCT00671736).

Estimation of Proinflammatory Factors in the Saliva of Adult Patients with Cystic Fibrosis and Dental Caries.

Introduction: The available literature lacks data regarding the levels of resistin, lysozyme, lactoferrin, α-amylase activity, pH, and saliva buffer capacity, as well as oral health and hygiene in the group of adult patients with cystic fibrosis (CF). The aim of the research was to assess the selected saliva parameters in patients diagnosed with cystic fibrosis. Materials and methods: Examined group was composed of 40 patients diagnosed with CF, while the control group of 40 healthy individuals. Both groups underwent the same scheme of the assessment (DMT index, salivary pH, buffer capacity, analysis of total sialic acid, total protein estimation, lysozyme levels estimation, lactofferin levels measurement, α-amylase activity, estimation of the levels of resistin and TNF-α). Results: In the examined group, there were higher values of decayed teeth as well as values of sialic acid, total protein, lactoferrin, α-amylase, and TNF-α. However, mean lysozyme, and resistin levels, as well as pH and buffer capacity of the saliva, were lower. Conclusions: New diagnostic methods, including the evaluation of selected salivary biochemical parameters, may indicate the existence of factors predisposing to severe tooth decay in the study group. Appropriate preventive treatment to combat dental caries in adult patients with CF will significantly improve their comfort and life expectancy.

Assessment of Selected Parameters of Liver Fibrosis and Inflammation in Patients with Diagnosed Cystic Fibrosis.

Changes in the liver and bile ducts observed in patients diagnosed with cystic fibrosis result from inflammatory processes as well as fibrosis, remodeling, apoptosis, and cholestasis. As a consequence, portal hypertension, cirrhosis, and hepatic failure may develop. So far, the complexity of these processes has not been elucidated. Study Objectives. The aim of the study was to evaluate the selected parameters of hepatitis and fibrosis (Fibrotest, Actitest, and APRI) in patients diagnosed with cystic fibrosis. Material and Methods. The study included 79 patients with cystic fibrosis, aged 1 to 20 years (mean age 9.8 years), 49 girls (62%) and 30 boys (38%). The analysis involved the following: age, sex, clinical manifestations, laboratory tests evaluating pancreas function, parameters of liver damage, and cholestasis. Fibrotest, Actitest, and APRI were performed in all subjects. Results. Elevated parameters of hepatic cell damage (hypertransaminasemia) were found in 31/79 (39.2%) patients, while abnormal cholestasis parameters in 21/79 (26.6%). The abnormal results of Fibrotest were reported in 15% of patients (12/79), while of Actitest in 10% (8/79). In contrast, elevated APRI values were found in only 7.6% (6/79) of subjects. There was a statistically significant correlation between APRI and age (higher values were observed in younger children) and between Fibrotest and Actitest and pancreatic insufficiency (higher values were found in subjects without this abnormality). Moreover, Fibrotest values were significantly higher in girls. There was no correlation between Fibrotest, Actitest, and APRI values and the type of mutation. Conclusion. It appears that Fibrotest may be used as an early marker of liver fibrosis in patients with cystic fibrosis. Increased APRI values were only found in subjects with advanced hepatic lesions, most often in the form of portal hypertension.

Reduced Exercise Tolerance Does Not Always Mean Bronchial Asthma.

Reduced exercise tolerance in a patient in whom any heart diseases were preliminarily excluded suggests other frequent causes of effort-related symptoms, that is, exercise-induced bronchoconstriction, lack of training, or overweight. The presented case underscores the importance of comprehensive diagnostic workup in children with exercise-related symptoms.

Acute subglottic laryngitis. Etiology, epidemiology, pathogenesis and clinical picture.

In about 3% of children, viral infections of the airways that develop in early childhood lead to narrowing of the laryngeal lumen in the subglottic region resulting in symptoms such as hoarseness, abarking cough, stridor, and dyspnea. These infections may eventually cause respiratory failure. The disease is often called acute subglottic laryngitis (ASL). Terms such as pseudocroup, croup syndrome, acute obstructive laryngitis and spasmodic croup are used interchangeably when referencing this disease. Although the differential diagnosis should include other rare diseases such as epiglottitis, diphtheria, fibrinous laryngitis and bacterial tracheobronchitis, the diagnosis of ASL should always be made on the basis of clinical criteria.

Prevalence and course of disease after lung resection in primary ciliary dyskinesia: a cohort & nested case-control study.

BACKGROUND: Lung resection is a controversial and understudied therapeutic modality in Primary Ciliary Dyskinesia (PCD). We assessed the prevalence of lung resection in PCD across countries and compared disease course in lobectomised and non-lobectomised patients. METHODS: In the international iPCD cohort, we identified lobectomised and non-lobectomised age and sex-matched PCD patients and compared their characteristics, lung function and BMI cross-sectionally and longitudinally. RESULTS: Among 2896 patients in the iPCD cohort, 163 from 20 centers (15 countries) underwent lung resection (5.6%). Among adult patients, prevalence of lung resection was 8.9%, demonstrating wide variation among countries. Compared to the rest of the iPCD cohort, lobectomised patients were more often females, older at diagnosis, and more often had situs solitus. In about half of the cases (45.6%) lung resection was performed before presentation to specialized PCD centers for diagnostic work-up. Compared to controls (n = 197), lobectomised patients had lower FVC z-scores (- 2.41 vs - 1.35, p = 0.0001) and FEV1 z-scores (- 2.79 vs - 1.99, p = 0.003) at their first post-lung resection assessment. After surgery, lung function continued to decline at a faster rate in lobectomised patients compared to controls (FVC z-score slope: - 0.037/year Vs - 0.009/year, p = 0.047 and FEV1 z-score slope: - 0.052/year Vs - 0.033/year, p = 0.235), although difference did not reach statistical significance for FEV1. Within cases, females and patients with multiple lobe resections had lower lung function. CONCLUSIONS: Prevalence of lung resection in PCD varies widely between countries, is often performed before PCD diagnosis and overall is more frequent in patients with delayed diagnosis. After lung resection, compared to controls most lobectomised patients have poorer and continuing decline of lung function despite lung resection. Further studies benefiting from prospective data collection are needed to confirm these findings.

Polish Society of Allergology statement on the diagnosis and treatment of severe, difficult-to-control bronchial asthma.

Severe asthma requires at least high doses of inhaled corticosteroids (ICS) in combination with a long-acting ß-agonist (LABA) or systemic corticosteroids (SCS) for more than 50% of days/year to avoid loss of control, or remains uncontrolled despite the treatment described above. The diagnosis of severe asthma should be confirmed in a reference centre as it requires careful differential diagnosis and the exclusion of factors hindering the achievement of optimal control. Severe asthma represents a significant burden for the patient, their family and the healthcare system. This is due to the severity of the symptoms, drug costs, significant impairment of everyday functioning and life quality, and limitation in the professional work. In the case of ineffectiveness of the step 4 GINA treatment, the patient should be referred to a specialist centre to consider additional treatment, including anti-IgE receptor (omalizumab), anti-IL-5 receptor (mepolizumab), or an antibody directed against the α-subunit of receptor for IL-5 (benralizumab). In the case of severe asthma, intensification of therapy should first of all include biological therapy and not the use of SCS. Biological drugs are available in Poland as a part of the therapeutic programme for the treatment of severe asthma. In practice, the therapeutic programme may change with subsequent notices of the Ministry of Health and does not have to be consistent with the Summary of Product Characteristics for individual preparations. The current review presents the basic principles of differential diagnosis of severe asthma and the selection of the optimal biological therapy in Polish conditions.