ERS statement on paediatric long-term noninvasive respiratory support.

Long-term noninvasive respiratory support, comprising continuous positive airway pressure (CPAP) and noninvasive ventilation (NIV), in children is expanding worldwide, with increasing complexities of children being considered for this type of ventilator support and expanding indications such as palliative care. There have been improvements in equipment and interfaces. Despite growing experience, there are still gaps in a significant number of areas: there is a lack of validated criteria for CPAP/NIV initiation, optimal follow-up and monitoring; weaning and long-term benefits have not been evaluated. Therapeutic education of the caregivers and the patient is of paramount importance, as well as continuous support and assistance, in order to achieve optimal adherence. The preservation or improvement of the quality of life of the patient and caregivers should be a concern for all children treated with long-term CPAP/NIV. As NIV is a highly specialised treatment, patients are usually managed by an experienced paediatric multidisciplinary team. This statement written by experts in the field of paediatric long-term CPAP/NIV aims to emphasise the most recent scientific input and should open up new perspectives and research areas.

Mycoplasma pneumoniae P1 Genotype Indicates Severity of Lower Respiratory Tract Infections in Children.

Mycoplasma pneumoniae strains can be classified into two major genetic groups, P1 type 1 (P1-1) and P1 type 2 (P1-2). It remains unknown if clinical manifestations of lower respiratory tract infections (LRTI) in children differ between the two genotypes. We aimed to determine if the M. pneumoniae P1 genotype is associated with severity of LRTI in children. Medical charts of 420 children (≤15 years old) with signs of acute LRTI who were PCR positive for M. pneumoniae from pharyngeal swabs in a recent M. pneumoniae epidemic were analyzed. We used a culture and pyrosequencing approach for genotyping PCR-positive samples. We compared epidemiological and clinical data of children with either P1-1 or P1-2 LRTI. P1-2-infected children presented with a significantly higher median baseline C-reactive protein level and were admitted to the hospital more often. The P1 genotype had a significant predictive value in a multiple linear regression model predicting C-reactive protein levels in our study sample. Moreover, the P1 genotype significantly affected the likelihood of hospital admission in a logistic regression model. Our modeling results were also confirmed on an additional independent sample of children with M. pneumoniae LRTI. Results from our large patient group indicate that the two M. pneumoniae P1 genotypes may have different pathogenic potential and that LRTI with P1-2 strains may have a more severe disease course than those with P1-1 strains in children. P1 genotyping is not routinely performed but could be used as a predictor of M. pneumoniae LRTI severity, enabling patient-tailored treatments.

Clinical characteristics of infections caused by Mycoplasma pneumoniae P1 genotypes in children.

Mycoplasma pneumoniae (M. pneumoniae) isolates can be classified into two major genetic groups, P1 type 1 (MP1) and P1 type 2 (MP2), based on the DNA sequence of the P1 adhesion protein gene. The aim of our study was to determine if M. pneumoniae P1 genotype is associated with disease manifestation and severity of acute M. pneumoniae infection. We compared epidemiological and clinical data of children infected with either MP1 or MP2. In addition, we separately analysed data of patients presenting with individual manifestations of M. pneumoniae infection. Data of 356 patients infected with MP1 were compared with those of 126 patients infected with MP2. MP2-infected children presented with higher median baseline C-reactive protein levels and were admitted to the hospital more often. The distribution of P1 genotype varied among groups of patients with different manifestations of M. pneumoniae infection. MP2 was more common than MP1 among patients with neurological and cardiovascular manifestations, whereas MP1 was more prevalent in other manifestations. The results from our large cohort indicate that the two P1 subtypes may have different pathogenic potential and that infections with MP2 strains could be more virulent than those with MP1 strains.

Assessment of serology and spirometry and the combination of both to complement microbiological isolation for earlier detection of Pseudomonas aeruginosa infection in children with cystic fibrosis.

BACKGROUND: The aim of this study was to assess whether serology and spirometry and the combination of both can complement culture-based detection for earlier recognition of Pseudomonas aeruginosa infection in children with cystic fibrosis. METHODS: A 4 year longitudinal prospective study that included 67 Slovenian children with cystic fibrosis with a mean age of 10.5 years was conducted. Serology, spirometry and a scoring system combining serology and spirometry were assessed and compared. Infection was confirmed with isolation of Pseudomonas aeruginosa from respiratory samples. RESULTS: There was a significantly positive correlation between serology and the combination of serology and spirometry and Pseudomonas aeruginosa isolation (P < 0.01 for both) and a significantly negative correlation between spirometry and Pseudomonas aeruginosa isolation (P < 0.05). An increase in serology for 1 ELISA unit increased the possibility of Pseudomonas aeruginosa isolation 1.6 times. A fall in FEV1% predicted for 10% increased the possibility of Pseudomonas aeruginosa isolation 9.8 times. Binary logistic regression analysis was used to determine the odds ratios and 95% confidence intervals for all three approaches. Serology had the highest specificity (0.80) and the combination of serology and spirometry the highest sensitivity (0.90). Both had a high negative predictive value (0.93 and 0.79 respectively). CONCLUSION: Using serology and the combination of serology and lung function measurement can be beneficial for earlier detection of infection with Pseudomonas aeruginosa in children with cystic fibrosis when done simultaneously with standard culture-based detection from respiratory samples.

First recovery of Rasamsonia argillacea species complex isolated in adolescent patient with cystic fibrosis in Slovenia--case report and review of literature.

We report the isolation of the emerging fungal pathogen Rasamsonia aegroticola, which belongs Rasamsonia argillacea species complex, from a respiratory sample of a patient with cystic fibrosis. This filamentous fungus, resembling members of a Penicillium and Paecilomyces spp., was identified by morphology and confirmed by DNA sequence analysis. Susceptibility pattern showed high minimal inhibitory concentration of voriconazole and amphotericin B but low minimal inhibitory concentration of caspofungin, micafungin and itraconazole.

Factors associated with FEV1 decline in cystic fibrosis: analysis of the ECFS patient registry.

Pulmonary insufficiency is the main cause of death in cystic fibrosis (CF). We analysed forced expiratory volume in 1 s (FEV1) data of 14,732 patients registered in the European Cystic Fibrosis Society Patient Registry (ECFSPR) database in 2007. We used linear and logistic regressions to investigate associations between FEV1 % predicted and clinical outcomes. Body mass index (BMI), chronic infection by Pseudomonas aeruginosa, pancreatic status and CF-related diabetes (CFRD) showed a statistically significant (all p<0.0001) and clinically relevant effect on FEV1 % pred after adjusting for age. Patients with a lower BMI experience a six-fold increased odds ratio (95% CI 5.0-7.3) of having severe lung disease (FEV1 <40% pred) compared to patients with normal BMI. Being chronically infected with P. aeruginosa increases the odds ratio of severe lung disease by 2.4 (95% CI 2.0-2.7), and patients with pancreatic insufficiency experience a 2.0-fold increased odds ratio (95% CI 1.6-2.5) of severe lung disease compared to pancreatic sufficient patients. Patients with CFRD have a 1.8-fold increased odds ratio (95% CI 1.6-2.2) compared to patients not affected. These potential risk factors for pulmonary disease in patients with CF are to some degree preventable or treatable. We emphasise the importance of their early identification through frequent routine tests, the implementation of infection control measures, and a timely initiation of relevant therapies.

Influence of anti-asthmatic medications on dental caries in children in Slovenia.

OBJECTIVE. The study investigated the influence of exposure to anti-asthmatic medications and of various factors on the caries prevalence in children in Slovenia. METHODS. The study population consisted of children aged 2 to 17 years (n = 220) under treatment for asthma, who had used anti-asthmatic medications for at least 1 year; 220 controls were matched for age. Caries status was determined by the number of decayed, missing, and filled surfaces through clinical examination by two calibrated dentists using the International Caries Detection and Assessment System-II scoring criteria. Questionnaires completed by parents and data from the patients' medical records provided information on various confounding factors. RESULTS. Asthmatic children had significantly higher (P ≤ 0.01) prevalence of caries on primary and permanent teeth in all age groups, and the proportion of caries-free children was significantly smaller (P ≤ 0.05). In multivariate regression analysis, asthma diagnosis, child's age, daily use of inhaled glucocorticoids, length and frequency of medicine application, spacer use, mouth rinsing with water after medicine application, parents' education, frequent food and drink consumption, and frequency of toothbrushing were associated with caries experience of asthmatic children. CONCLUSION. Children with asthma who had used anti-asthmatic medications had higher caries experience in primary and permanent teeth.

Clinical, Laboratory, and Radiographic Features Can Help Predict Mycoplasma pneumoniae Lower Respiratory Tract Infection in Children.

Mycoplasma pneumoniae (Mp) is a common cause of lower respiratory tract infection (LRTI) in children that is difficult to distinguish from LRTI of other etiologies. We aimed to determine if a combination of clinical, laboratory, and chest radiographic features can help identify patients at higher risk of Mp LRTI. We reviewed medical charts of children referred to our tertiary hospital with suspected acute mycoplasmal LRTI. Pharyngeal swabs obtained from patients were tested by Mp PCR. We compared epidemiological and clinical data of children with positive and negative Mp PCR results. In addition, a multivariable logistic regression analysis was performed to predict Mp LRTI based on the patient's age, duration of symptoms, presence of extrapulmonary manifestations, laboratory findings, and chest radiographic findings. We included 65 children with Mp PCR-negative and 49 with Mp PCR-positive LRTI and no viral co-detection. Children with Mp LRTI were older (median age 5.8 vs. 2.2 years, p < 0.001), had a longer duration of symptoms on referral (median 7 vs. 4 days, p < 0.001), and lower median WBC (9.9 vs. 12.7 × 109/L, p < 0.001). On chest radiograph, unilateral infiltrates were more frequently observed in the Mp PCR-positive group (57.5% vs. 24.1%, p = 0.001). Age, duration of symptoms, and chest radiographic findings had the highest predictive value for Mp LRTI in a multivariable logistic regression model. Our analysis suggests that a combination of clinical, laboratory, and chest radiographic features can be used to assess the likelihood of Mp LRTI and assist in decision-making for which children need further tests or macrolide antibiotic treatment.

Physical fitness trajectories from childhood to adolescence in extremely preterm children: A longitudinal cohort study.

OBJECTIVE: Cohort studies on physical fitness (PF) in former extremely preterm children are scarce and yield conflicting results. Therefore, this study aimed to assess the effect of extremely preterm birth on PF in school-age with a focus on bronchopulmonary dysplasia (BPD). METHODS: Eighty school-aged children were enrolled in the longitudinal cohort study. Fifty were born extremely preterm (

Risk factors for forced expiratory volume in 1 s decline in European patients with cystic fibrosis: data from the European Cystic Fibrosis Society Patient Registry.

Aim: To examine the trajectory of forced expiratory volume in 1 s (FEV1) using data from the European Cystic Fibrosis Society patient registry (ECFPR) collected from 2008 to 2016, i.e. the era before highly effective modulator therapy (HEMT). We evaluated risk factors for FEV1 decline. Methods: The study population included patients with a confirmed diagnosis of cystic fibrosis recorded in the ECFPR (2008-2016). The evolution of FEV1 % predicted (%FEV1) with age, and the yearly change in %FEV1 were evaluated. Risk factors considered were cystic fibrosis transmembrane conductance regulator (-CFTR) mutation class, gender, age at diagnosis, neonatal screening, meconium ileus, sweat chloride concentration at diagnosis and country's income level. Results: We used 199 604 FEV1 recordings from 38 734 patients. The fastest decline was seen during puberty and in patients diagnosed before the age of 10 years. Males had a higher %FEV1, but a higher yearly %FEV1 loss between the ages of 15 and 25 years. We showed stabilisation and even improvement in %FEV1 over age in adults with a class III CFTR mutation, but a steady decline in patients homozygous for F508del or with both mutations of classes I/II. A faster decline in %FEV1 was found in patients from low-income countries compared to a similar %FEV1 evolution in patients from middle- and high-income countries. Conclusions: These longitudinal FEV1 data reflect the reality of cystic fibrosis across Europe in the era pre-HEMT, and can serve as baseline for comparison with the post-HEMT era. The similar evolution in middle- and high-income countries underlines opportunities for low-income countries.

SARS-CoV-2-related bronchiolitis: a multicentre international study.

BACKGROUND: Bronchiolitis is the main acute lower respiratory tract infection in infants. Data regarding SARS-CoV-2-related bronchiolitis are limited. OBJECTIVE: To describe the main clinical characteristics of infants with SARS-CoV-2-related bronchiolitis in comparison with infants with bronchiolitis associated with other viruses. SETTING, PATIENTS, INTERVENTIONS: A multicentre retrospective study was conducted in 22 paediatric emergency departments (PED) in Europe and Israel. Infants diagnosed with bronchiolitis, who had a test for SARS-CoV-2 and were kept in clinical observation in the PED or admitted to hospital from 1 May 2021 to 28 February 2022 were considered eligible for participation. Demographic and clinical data, diagnostic tests, treatments and outcomes were collected. MAIN OUTCOME MEASURES: The main outcome was the need for respiratory support in infants testing positive for SARS-CoV-2 compared with infants testing negative. RESULTS: 2004 infants with bronchiolitis were enrolled. Of these, 95 (4.7%) tested positive for SARS-CoV-2. Median age, gender, weight, history of prematurity and presence of comorbidities did not differ between the SARS-CoV-2-positive and SARS-CoV-2-negative infants. Human metapneumovirus and respiratory syncytial virus were the viruses most frequently detected in the group of infants negative for SARS-CoV-2.Infants testing positive for SARS-CoV-2 received oxygen supplementation less frequently compared with SARS-CoV-2-negative patients, 37 (39%) vs 1076 (56.4%), p=0.001, OR 0.49 (95% CI 0.32 to 0.75). They received less ventilatory support: 12 (12.6%) high flow nasal cannulae vs 468 (24.5%), p=0.01; 1 (1.0%) continuous positive airway pressure vs 125 (6.6%), p=0.03, OR 0.48 (95% CI 0.27 to 0.85). CONCLUSIONS: SARS-CoV-2 rarely causes bronchiolitis in infants. SARS-CoV-2-related bronchiolitis mostly has a mild clinical course.

Human bocavirus and other respiratory viral infections in a 2-year cohort of hospitalized children.

Human bocavirus (HBoV) infection is reported worldwide and may cause severe respiratory tract infections. The aim of the present study was to assess the prevalence of HBoV, and other respiratory viral pathogens, in a 2-year retrospective study of children admitted to hospital, and to investigate whether viral loads of HBoV DNA were associated with severity of infection. Between April 2007 and March 2009, 891 respiratory samples from 760 children admitted to hospital with acute respiratory tract infection were tested for the presence of respiratory viruses by real-time PCR or direct immunofluorescence testing. HBoV DNA was detected by using internally controlled real-time quantitative PCR assay and 25 samples selected at random were sequenced. The virus detected most frequently was rhinovirus, followed by respiratory syncytial virus, HBoV, and human metapneumovirus. HBoV DNA was detected in 18.4% of children admitted to hospital. HBoV was the only viral pathogen detected in 66/164 (40.2%) of HBoV DNA-positive children and in 7.4% of all 891 samples. Ninety-seven percent (64/66) of children with an HBoV single infection were diagnosed as having lower respiratory tract infection. Median HBoV DNA viral load was significantly higher in children when HBoV was detected as a single pathogen. Higher HBoV DNA viral loads were associated with prematurity and age. HBoV seems to be an important and frequent pathogen in respiratory tract infections in children, and it is likely that the severity of illness is comparable to the severity of RSV illness.

Coronavirus infections in hospitalized pediatric patients with acute respiratory tract disease.

BACKGROUND: Acute viral respiratory infections are an important cause of morbidity and mortality in humans worldwide. The etiological backgrounds of these infections remain unconfirmed in most clinical cases. The aim of this study was to estimate the prevalence of human coronavirus infections in a series of children hospitalized with symptoms of acute respiratory tract disease in a one-year period in Slovenia. METHODS: The 664 specimens from 592 children under six years of age hospitalized at the University Children's Hospital in Ljubljana were sent for the routine laboratory detection of respiratory viruses. Respiratory viruses were detected with a direct immunofluorescence assay and human coronaviruses were detected with a modified real-time RT-PCR. RESULTS: HCoV RNA was detected in 40 (6%, 95% CI: 4.3%-8.1%) of 664 samples. Of these specimens, 21/40 (52.5%) were identified as species HKU1, 7/40 (17.5%) as OC43, 6/40 (15%) as 229E, and 6/40 (15%) as NL63. Infection with HCoV occurred as a coinfection with one or more other viruses in most samples (70%). Of the HCoV-positive children, 70.3% had lower respiratory tract infections. CONCLUSION: The results of our study show that HCoV are frequently detected human pathogens, often associated with other respiratory viruses and acute respiratory tract infections in hospitalized children. An association between age and the viral load was found. The highest viral load was detected in children approximately 10 months of age.

Nocturnal hypoxemia, but not hypercapnia, correlates with sleep quality in children.

BACKGROUND: A correlation has been observed between obstructive sleep events and sleep quality. The aim of the study was to assess if there is also a correlation between nocturnal hypoxemia and hypercapnia and sleep efficiency and sleep fragmentation in children. METHODS: Nocturnal pulse oximetry (S(pO(2))) and transcutaneous carbon dioxide (P(tcCO(2))) recordings with simultaneous actigraphy were performed in 38 children with nocturnal hypoxemia and hypercapnia during spontaneous breathing (nocturnal hypoventilation [NH] group), 25 children with partially corrected nocturnal hypoventilation (PC-NH group), and 11 subjects with normal nocturnal gas exchange (no-NH group). RESULTS: Sleep efficiency and sleep fragmentation on actigraphy correlated with minimal S(pO(2)) (r(2) = 0.21, P = .004, and r(2) = -0.10, P = .050, respectively) and the percentage of night time with S(pO(2)) < 90% (r(2) = -0.33, P < .001, and r(2) = 0.13, P = .028, respectively) in the NH group. Sleep efficiency and sleep fragmentation also correlated with pulse rate standard deviation (r(2) = -0.42, P < .001, and r(2) = 0.37, P < .001, respectively). No correlation was observed between sleep efficiency and sleep fragmentation and P(tcCO(2)). No correlation was observed between sleep efficiency and sleep fragmentation and S(pO(2)), P(tcCO(2)), and pulse rate in the PC-NH group. Sleep efficiency, sleep fragmentation, and nocturnal S(pO(2)), and P(tcCO(2)) were all normal and not correlated in the no-NH group. CONCLUSIONS: In children with nocturnal hypoventilation, nocturnal hypoxemia but not hypercapnia correlates with sleep efficiency and sleep fragmentation on actigraphy.

Human bocavirus as the cause of a life-threatening infection.

Human bocavirus is a recently described respiratory pathogen. A case of a life-threatening human bocavirus infection of a previously healthy pediatric patient is described. An initial clinical presentation of acute bronchiolitis developed into an extremely severe course of disease characterized by pneumothorax, pneumomediastinum, and acute respiratory failure with pronounced air-leak syndrome.

Biologicals in childhood severe asthma: the European PERMEABLE survey on the status quo.

INTRODUCTION: Severe asthma is a rare disease in children, for which three biologicals, anti-immunoglobulin E, anti-interleukin-5 and anti-IL4RA antibodies, are available in European countries. While global guidelines exist on who should receive biologicals, knowledge is lacking on how those guidelines are implemented in real life and which unmet needs exist in the field. In this survey, we aimed to investigate the status quo and identify open questions in biological therapy of childhood asthma across Europe. METHODS: Structured interviews regarding experience with biologicals, regulations on access to the different treatment options, drug selection, therapy success and discontinuation of therapy were performed. Content analysis was used to analyse data. RESULTS: We interviewed 37 experts from 25 European countries and Turkey and found a considerable range in the number of children treated with biologicals per centre. All participating countries provide public access to at least one biological. Most countries allow different medical disciplines to prescribe biologicals to children with asthma, and only a few restrict therapy to specialised centres. We observed significant variation in the time point at which treatment success is assessed, in therapy duration and in the success rate of discontinuation. Most participating centres intend to apply a personalised medicine approach in the future to match patients a priori to available biologicals. CONCLUSION: Substantial differences exist in the management of childhood severe asthma across Europe, and the need for further studies on biomarkers supporting selection of biologicals, on criteria to assess therapy response and on how/when to end therapy in stable patients is evident.

Factors for severe outcomes following SARS-CoV-2 infection in people with cystic fibrosis in Europe.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with cystic fibrosis (pwCF) can lead to severe outcomes. METHODS: In this observational study, the European Cystic Fibrosis Society Patient Registry collected data on pwCF and SARS-CoV-2 infection to estimate incidence, describe clinical presentation and investigate factors associated with severe outcomes using multivariable analysis. RESULTS: Up to December 31, 2020, 26 countries reported information on 828 pwCF and SARS-CoV-2 infection. Incidence was 17.2 per 1000 pwCF (95% CI: 16.0-18.4). Median age was 24 years, 48.4% were male and 9.4% had lung transplants. SARS-CoV-2 incidence was higher in lung-transplanted (28.6; 95% CI: 22.7-35.5) versus non-lung-transplanted pwCF (16.6; 95% CI: 15.4-17.8) (p≤0.001).SARS-CoV-2 infection caused symptomatic illness in 75.7%. Factors associated with symptomatic SARS-CoV-2 infection were age >40 years, at least one F508del mutation and pancreatic insufficiency.Overall, 23.7% of pwCF were admitted to hospital, 2.5% of those to intensive care, and regretfully 11 (1.4%) died. Hospitalisation, oxygen therapy, intensive care, respiratory support and death were 2- to 6-fold more frequent in lung-transplanted versus non-lung-transplanted pwCF.Factors associated with hospitalisation and oxygen therapy were lung transplantation, cystic fibrosis-related diabetes (CFRD), moderate or severe lung disease and azithromycin use (often considered a surrogate marker for Pseudomonas aeruginosa infection and poorer lung function). CONCLUSION: SARS-CoV-2 infection yielded high morbidity and hospitalisation in pwCF. PwCF with forced expiratory volume in 1 s <70% predicted, CFRD and those with lung transplants are at particular risk of more severe outcomes.

Noninvasive Ventilation in Palliative Care and Ethical Dilemma.

Significant difference exists between validated indications for noninvasive ventilation (NIV) use in children and current real life practice. Lately, dedicated centers have reported exponential growth of NIV use in children and adolescents. Upper airway obstruction, neuromuscular diseases, chronic lung/thoracic conditions, and central respiratory drive failure remain the most prevalent indications. However, the need to alleviate respiratory failure related distress has been increasingly recognized in several other conditions. Palliative care in children with life limiting disorders is a complex continuum of activities. In order to provide the most appropriate care for the patients and their families, the management often oscillates between actively curative and purely supportive actions. Despite unprecedented therapeutic advancements, several neurologic, metabolic, hemato-oncologic, respiratory, and other rare diseases remain with no curative options. Besides, attentiveness to relive suffering, awareness, and availability have moved the boundaries of NIV use toward conditions formerly not considered suitable for such care. Still, NIV has limitations and can, if sustained in inappropriate circumstances, fail to provide relief. A structured professional frameshift should be available for support and ethical guidance in order to provide confidence to patients, families and all the involved caregivers.

Non-invasive Ventilation for Children With Chronic Lung Disease.

Advances in medical care and supportive care options have contributed to the survival of children with complex disorders, including children with chronic lung disease. By delivering a positive pressure or a volume during the patient's inspiration, NIV is able to reverse nocturnal alveolar hypoventilation in patients who experience hypoventilation during sleep, such as patients with chronic lung disease. Bronchopulmonary dysplasia (BPD) is a common complication of prematurity, and despite significant advances in neonatal care over recent decades its incidence has not diminished. Most affected infants have mild disease and require a short period of oxygen supplementation or respiratory support. However, severely affected infants can become dependent on positive pressure support for a prolonged period. In case of established severe BPD, respiratory support with non-invasive or invasive positive pressure ventilation is required. Patients with cystic fibrosis (CF) and advanced lung disease develop hypoxaemia and hypercapnia during sleep and hypoventilation during sleep usually predates daytime hypercapnia. Hypoxaemia and hypercapnia indicates poor prognosis and prompts referral for lung transplantation. The prevention of respiratory failure during sleep in CF may prolong survival. Long-term oxygen therapy has not been shown to improve survival in people with CF. A Cochrane review on the use NIV in CF concluded that NIV in combination with oxygen therapy improves gas exchange during sleep to a greater extent than oxygen therapy alone in people with moderate to severe CF lung disease. Uncontrolled, non-randomized studies suggest survival benefit with NIV in addition to being an effective bridge to transplantation. Complications of NIV relate mainly to prolonged use of a face or nasal mask which can lead to skin trauma, and neurodevelopmental delay by acting as a physical barrier to social interaction. Another associated risk is pulmonary aspiration caused by vomiting whilst wearing a face mask. Adherence to NIV is one of the major barriers to treatment in children. This article will review the current evidence for indications, adverse effects and long term follow up including adherence to NIV in children with chronic lung disease.

The c.3140-26A>G Variant of the CFTR Gene in Homozygous State Causes Mild Cystic Fibrosis - Overview of Longitudinal Clinical Data of the Patient Managed in our CF Center and Review of the Literature.

There are over 70.000 patients with cystic fibrosis (CF) in the world and numerous sequence variations in the CFTR gene have been reported but the clinical significance of all of them is still not known. There are currently 195 patients with the c.3140-26A>G (legacy name 3272-26A>G) variant in the CFTR gene listed in the European Cystic Fibrosis Society Patient Registry (ECFSPR) and only 4 are homozygous. We present longitudinal clinical data of one of these patients who is managed in our CF Center at the University Children's Hospital in Ljubljana and compare it with the patient data from the ECFSPR and the CFTR2 database in which additional 3 homozygous patients are described. Moreover, the effect of the detected variant in the described patient was evaluated on the RNA level in nasal epithelial cells. The variant was shown to result in aberrant splicing introducing a frameshift and a premature termination codon while normal transcript was not detected. Alternative spliced mutant transcripts in other tissues or the presence of spliceosome-mediated RNA trans-splicing could explain the mild clinical presentation of patients with this variant in homozygous state.