Cistična fibroza (CF) je najpogostejša avtosomno recesivna genetska bolezen, pri kateri so prizadeti številni organski sistemi, predvsem dihala, prebavila, endokrini sistem in reproduktivni organi. Določene morfološke spremembe pri plodu lahko odkrijemo že pred rojstvom. Po rojstvu lahko zaradi zapore prebavil ob mekonijskem ileusu pride do življenje ogrožujočih zapletov. Bolezen se najpogosteje klinično izrazi v zgodnjem otroštvu, vendar ima lahko že novorojenček pomanjkljivo delovanje trebušne slinavke. CF pri novorojenčkih odkrivamo s presejalnim testiranjem. Poleg dosedanje obravnave, ki pri bolnikih s CF vključuje respiratorno fizioterapijo, aktivno iskanje in zdravljenje okužb, skrb za primerno prehranjenost ter nadomeščanje encimov, vitaminov in mineralov, pa se je zaradi uvedbe novejših zdravil (modulatorjev regulatorja transmembranske prevodnosti pri CF oz. CFTR modulatorjev) močno spremenil potek bolezni in se izboljšala reproduktivna sposobnost žensk. Ker na potek nosečnosti zaenkrat ni dokazanega pomembnega negativnega vpliva, noseče bolnice pogosto nadaljujejo z zdravljenjem tudi med nosečnostjo. CFTR modulatorji prehajajo preko posteljice in se izločajo z materinim mlekom. Ker je ob odkritju bolezni pri novorojenčku potrebna obravnava, smo izdelali priporočila. V prispevku opisujemo tudi pogled na zdravljenje ploda s CF že prenatalno in obravnavo novorojenčka, ki je bil kot plod izpostavljen zdravilom za CF zaradi zdravljenja matere s CF med nosečnostjo.

Cystic fibrosis (CF) is the most common autosomal recessive genetic disorder, affecting multiple organ systems, primarily the respiratory, digestive, endocrine and reproductive systems. Morphological changes in the fetus can be detected antenatally. After birth, life-threatening complications may occur due to intestinal obstruction caused by meconium ileus. The disease usually presents clinically in early childhood, although pancreatic insufficiency may already be present in newborns. CF is diagnosed in newborns through screening programmes. In addition to respiratory physiotherapy, early detection and treatment of infections, appropriate nutrition, and replacement therapy with enzymes, vitamins and minerals, the introduction of newer medications (CF transmembrane conductance regulator [CFTR] modulators) has significantly altered the course of the disease and improved female reproductive potential. As these medications have not been shown to have significant adverse effects on pregnancy, patients often continue treatment during pregnancy. CFTR modulators cross the placenta and are excreted into breast milk. As treatment is required upon diagnosis in a newborn, we have developed recommendations. This article also provides an overview of the prenatal management of a fetus with CF and the management of a newborn exposed to CFTR mod-ulators in utero as a result of maternal treatment during pregnancy.

BACKGROUND:Highly effective CFTR modulator therapy, such as elexacaftor/tezacaftor/ivacaftor (ETI), has been linked to significant clinical improvements in people with cystic fibrosis (pwCF). However, its effect on the presence of respiratory pathogens in the lower respiratory tract of younger, mainly non-expectorant children with CF remains poorly understood, especially using lower airway sampling methods. We aimed to investigate changes in lower airway microbiology and clinical outcomes in children with CF aged 6-12 years before and after starting ETI. METHODS:We conducted a prospective observational single-centre study including children with CF commencing ETI who had no prior exposure to CFTR modulators, inhaled antibiotics, or prophylactic antibiotics. Lower airway microbiology was assessed longitudinally using sputum or induced sputum (IS). Pathogen prevalence, sweat chloride concentration, pulmonary function, nutritional status, and rate of exacerbations were evaluated before and up to 12 months after ETI initiation. RESULTS:Sixteen pwCF were included (median age 8.4 years, 69 % boys, 75% were F508del homozygous). None of the children was expectorant at any point during the study. Following ETI initiation, we observed decreased growth of methicillin-sensitive Staphylococcus aureus and Aspergillus fumigatus, reduced variability in fungal populations, and an increase in negative bacterial and fungal culture results. CONCLUSIONS:In this exploratory study of young, modulator-naïve children with CF, ETI initiation was associated with changes in the lower airway microbiology composition assessed by IS. These findings highlight potential shifts in lower airway microbiology and the importance of age-appropriate lower airway sampling in future paediatric studies.

BACKGROUND:Post-infectious bronchiolitis obliterans (PIBO) is a rare chronic pediatric pulmonary disease characterized by irreversible fibrotic narrowing of the small airways. Treatment options remain uncertain with limited success. OBJECTIVE:To delineate the characteristics of patients diagnosed with PIBO in Ljubljana (Slovenia) and Trieste (Italy) in 2023. METHODS:We retrospectively assessed clinical records of PIBO patients from January to December 2023, capturing data on initial viral infection, clinical presentation, radiological features, treatments, and outcomes. RESULTS:In 2023, 11 patients were identified, contrasting with only 6 cases in the previous 7 years. Common symptoms and signs included tachypnea, chronic wet cough, and diffuse crackles following adenovirus pneumonia. Most patients were previously healthy. Chest CT findings confirmed the diagnosis in all cases. Bronchoalveolar lavage showed elevated levels of neutrophils (46% to 90% of cells), and biopsies performed in 6 patients indicated predominantly lymphocytic inflammatory infiltrate and bronchiolar fibrosis. Nocturnal pulse oximetry revealed reduced mean SpO2 (median: 96.5% Q1: 93%, Q3: 98%) and reduced lower values (median: SpO2 89% Q1: 87%, Q3: 92.5%) with an increased oxygen desaturation index (1.1 to 11.2 events/hour). Treatment involved methylprednisolone (20-30 mg/kg) for three consecutive days monthly for 6 months, resulting in clinical improvement in nine patients and radiological improvement in seven patients. CONCLUSIONS:The post-pandemic surge in PIBO cases may stem from viral ecology changes, immunologic factors, and/or adenovirus genotypes, highlighting the need for further research into its etiology and management strategies.

Oesophageal atresia, with or without tracheoesophageal fistula, is a congenital malformation of the digestive tract. Despite surgical repair, patients often experience problems that affect multiple organ systems and significantly impair their quality of life. This article provides an overview of short- and long-term complications following oesophageal atresia surgery and other health problems related to the dysfunction of the affected organs. In addition, we emphasise the importance of multidisciplinary follow-up for these children to improve the detection, prevention and treatment of their health problems and improve their quality of life.

Atrezija požiralnika s traheoezofagealno fistulo ali brez nje je prirojena razvojna nepravilnost prebavne cevi. Po kirurški ureditvi nepravilnosti imajo bolniki lahko težave v več organskih sistemih, kar pomembno vpliva na kakovost življenja. V članku želimo prikazati kratkoročne in dolgoročne zaplete po kirurški ureditvi atrezije požiralnika ter druge zdravstvene težave, povezane z moteno zgradbo in delovanjem prizadetih organov. Želimo poudariti, kako pomembno je, da te otroke spremlja multidisciplinarni tim za izboljšanje prepoznave, preprečevanja in zdravljenja težav ter izboljšanja kakovosti življenja teh otrok.

IntroductionEnterovirus D68 (EV-D68) belongs to the Picornaviridae family, genus Enterovirus. It is mostly known as a respiratory virus causing upper and lower respiratory tract infections, but it is also rarely associated with a variety of central nervous system complications, with acute flaccid myelitis being reported most frequently. This study assesses the incidence, seasonality, clinical presentation, and molecular epidemiology of the EV-D68 strain in EV-positive children hospitalized between 2014 and 2022 at the largest pediatric medical center in Slovenia.MethodsEV-D68 was detected using specific qRT-PCR, whereas partial VP1 sequences were obtained with Sanger sequencing, and further analyzed using the software CLC Main Workbench version 7 and MEGA version X.ResultsEV-D68 was detected in 154 out of 1,145 (13.4%) EV-positive children. In the two epidemic years, 2014 and 2016, EV-D68 was most frequently detected in the summer and early autumn, peaking in September. The median age of EV-D68–infected children was 3 years (IQR 1–3 years), with a female: male ratio of 1:1.17. Rhinorrhea was present in 74.0% of children, respiratory distress in 82.5%, and hypoxemia requiring supplemental oxygen in 44.1%. Out of 154 patients, 80.0% were hospitalized, with a median stay of 2 days (IQR 1–3 days). Lower respiratory tract infection was observed in 89.0% of EV-D68–positive patients, with bronchitis and bronchiolitis being most frequently diagnosed. No central nervous system manifestations of EV-D68 infection were observed in the study cohort. Phylogenetic analysis of partial VP1 sequences of EV-D68 revealed close similarity to the EV-D68 variants that were circulating in other European countries in these years.DiscussionSlovenia faced two EV-D68 epidemics in 2014 and 2016; however, after 2016 only nine more cases were detected until the end of the study period. Based on the results of this study, EV-D68 was a frequent cause of lower respiratory tract infection among EV-positive patients. However, none of the patients we studied needed ICU treatment, and none developed acute flaccid paralysis. Our results indicate that EV-D68 is not present constantly, so additional monitoring studies should be conducted in the future to better understand the implications of this EV type in human disease.

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.