Thymic stromal lymphopoietin (TSLP), an epithelium-derived pro-inflammatory cytokine, activates distinct immune and non-immune cells. It has been shown to be a master regulator of type 2 immune ...responses. Limited information is available on TSLP in childhood asthma. The aim of the present study was to find out whether there is association between TSLP concentrations and asthma phenotypes or disease activity.
A total of 207 children with asthma and 100 healthy children aged 1–13 years were enrolled. This study examined serum TSLP concentrations using ELISA Kit in asthma patients and controls, analyzed its correlation with asthma phenotypes and pulmonary function. We also examined TSLP concentrations in 23 patients during stable asthma and in acute asthma exacerbation.
The serum concentrations of TSLP were significantly elevated in asthma patients compared with healthy controls (p < 0.05), but there was no significant difference (p > 0.05) in TSLP concentrations between three different asthma phenotypes (allergic asthma, virus induced asthma and nonallergic asthma). There was no significant correlation between TSLP concentrations and FEV1pred% (r = 0.01, p > 0.05).
In the acute asthma exacerbation TSLP concentrations were not significantly different than in stable phase of disease (p > 0.05).
Children with asthma have higher serum TSLP concentrations when compared to healthy controls. TSLP does not seem to be a biomarker of disease exacerbation in children. Different asthma phenotypes have similar TSLP concentration profile in peripheral blood and TSLP does not seem to be useful biomarker in asthma phenotyping in children.
•The thymic stromal lymphopoietin is a master regulator of type 2 immune responses.•Serum TSLP concentrations are higher in children with asthma.•TSLP role in identifying children with different asthma phenotypes is limited.•Serum TSLP does not seem to be a biomarker of asthma exacerbation.
Spontaneous pneumomediastinum is a rare clinical entity defined as the presence of free air in the mediastinal structures without an apparent cause such as trauma. Spontaneous pneumomediastinum is ...rare in children and most frequently occurs in young male patients. It usually develops after alveolar rupture and air penetration into the pulmonary interstice, followed by air penetration towards the hila and into the mediastinum. Alveolar ruptures may be caused by various pathological and physiological processes, in children most frequently by asthma. Clinical diagnosis is based on the symptom triad including chest pain, dyspnea and subcutaneous emphysema. The diagnosis is confirmed by radiography. On differential diagnosis, esophageal perforation should be considered first, and if suspected, contrast esophagogram should be performed. Spontaneous pneumomediastinum usually resolves spontaneously in several days of treatment, which includes identification of the underlying cause (if possible), rest, analgesics and clinical monitoring. Complications involving spontaneous pneumomediastinum, such as tension pneumomediastinum and tension pneumothorax, are quite rare. A case is presented of pneumomediastinum in a 17-year-old male adolescent with no relevant history but with a clinical picture of intense retrosternal pain and subcutaneous emphysema of the neck and supraclavicular region. Thorough examinations including chest x-ray, chest computed tomography, bronchoscopy and esophagoscopy failed to identify the cause of pneumomediastinum. After eight days of conservative treatment, the pneumomediastinum symptoms completely disappeared and x-ray showed resolution of pneumomediastinum.
Community-acquired bacterial pneumonias generally have a good prognosis, given a good response to the antibiotic treatment applied, and complications such as pleural effusion, empyema, abscess and ...necrotizing pneumonia with pneumatocele formation (cavitary necrosis) are rare. Although cavitary necrosis is manifested as a severe disease, most children show complete recovery even without surgical treatment and have normal chest radiographs at long term. A case is presented of an immunocompetent infant that developed necrotizing pneumonia with pneumatocele formation during treatment of bacterial pneumonia. Conservative treatment led to complete regression of necrotic cavities and resulted in normal chest radiography finding 2.5 months of the occurrence of pneumatoceles.
Asthma is the most prevalent chronic disorder of childhood. In a large number of cases, it can be well managed. In addition to accurate diagnosis, appropriate therapy and control of environmental ...factors, a good educational program is required, which has not yet received due attention. Prompted by the fact that a large number of asthmatic children and their parents lack sufficient knowledge about asthma, six years ago we launched an individual educational program for all asthmatic children over seven years of age and their parents. We monitored a group of 58 asthmatics, the first to have completed our individual educational program, during the year before and the year after they had received individual education. The prerequisites for inclusion in the study were that the child was over seven years of age, diagnosed with chronic asthma according to the GINA guidelines and had been monitored for one year prior to receiving individual education. We compared the number of asthma exacerbations, hospitalizations due to asthma, days with asthmatic symptoms, the mean value of the forced expiratory volume in 1 second (FEV 1), and the mean dose of inhaled corticosteroids (ICS) taken during the year before and the year after receiving individual education. Study results showed the number of asthma exacerbations (p < 0.0001), hospitalizations due to asthma (p = 0.0236) and days with asthmatic symptoms (p < 0.0001) to have significantly reduced, along with a significant increase in FEV 1 (p < 0.0001) and lower mean ICS dose (p < 0.0001) upon completion of individual educational program. It is concluded that the addition of individual education in the treatment of asthmatic children enables better control of the disease (lower number of hospitalizations and asthma exacerbations, increased FEV 1) with a lower mean ICS dose. The knowledge about asthma acquired by the children and their parents, self-management, compliance with the written asthma management plan, control of environmental factors, along with good cooperation of the patients and parents in the management of asthma certainly contributed to this favorable observation.
Izvanbolničke upale pluća u djece Pavlov, Neven; Banac, Srđan; Bralić, Irena ...
Liječnički vjesnik,
10/2021, Volume:
143, Issue:
9-10
Journal Article
Peer reviewed
Open access
Izvanbolnička upala pluća jest potencijalno ozbiljna infekcija u djece. Dijagnostika izvanbolničkih upala pluća u djece temelji se na anamnestičkim podatcima i kliničkim simptomima i znacima, ...potpomognuto dodatnim dijagnostičkim pretragama: laboratorijskim, slikovnim i mikrobiološkim. Etiologija izvanbolničke upale pluća ovisi o brojnim čimbenicima, kao što su sezonstvo, geografski položaj, dob bolesnika i težina bolesti. Liječenje djeteta s izvanbolničkom upalom pluća uključuje primjenu simptomatskih mjera i u većine bolesnika antimikrobnu terapiju. U radu su prikazane kliničke preporuke Hrvatskog društva za pedijatrijsku pulmologiju radi ujednačenja postupaka i kriterija postavljanja dijagnoze, liječenja i prevencije izvanbolničkih upala pluća u djece.
Background: Eighty percent of asthmatic children develop asthma symptoms by the age of 5 years. Inhaled corticosteroids (ICS), depending on dosage, may cause linear growth reduction and adrenal ...gland suppression. There are few studies about linear growth of preschool children with asthma. The aim of the present study was to investigate whether there is any effect of fluticasone propionate (FP) on linear growth and adrenal gland function.
Methods: Twenty‐eight children aged 18–52 months with persistent asthma receiving ICS FP 100–200 µg daily were studied for 1 year. Patients were divided into two groups according to clinical parameters: well (group 1) and poorly controlled (group 2). Height was measured every 3 months and expressed as height standard deviation score (SDS). Cumulative dose of FP expressed in mg was calculated for every patient. Early morning levels of serum adrenocorticotropic hormone (ACTH) and cortisol were assessed at the beginning and at the end of the study.
Results: Patients took FP for an average of 11 months in group 1 and 16 months in group 2, which was not statistically significantly different. At the end of the study height SDS difference was −0.0143 in group 1 and −0.2000 in group 2, which was not statistically significantly different (t= 0.6072, P= 0.5489). There was also no statistically significant difference for average cortisol (P= 0.4381) or ACTH (P= 0.5845) concentration at the end of the study.
Conclusion: FP 100–200 µg daily had no effect on linear growth or on the hypothalamic–pituitary–adrenal gland axis but further follow up is necessary.
Respiratory syncytial virus (RSV) is the most common cause of severe lower respiratory tract infection, with a high global health burden. There are no effective treatments available. ALX-0171 is a ...novel trivalent Nanobody with antiviral properties against RSV. We aimed to assess the safety and antiviral activity of nebulised ALX-0171 in children admitted to hospital with RSV lower respiratory tract infection.
This double-blind, randomised, placebo-controlled, phase 2b trial was done in 50 hospital paediatric departments across 16 countries. Previously healthy children aged between 28 days to younger than 24 months who were admitted to hospital with RSV acute severe lower respiratory tract infection were randomly assigned in three sequential safety cohorts (3:1) to receive nebulised ALX-0171 (cohort 1 received 3 mg/kg, cohort 2 received 6 mg/kg, and cohort 3 received 9 mg/kg) or placebo once daily for 3 days using web-based randomisation in the sequential safety part (first block size 12, subsequently four). In a parallel part of the study, participants (cohort 4) were randomly assigned (parallel 1:1:1:1) to receive nebulised ALX-0171 3 mg/kg, 6 mg/kg, 9 mg/kg, or placebo (blocks of eight by restricted randomisation). Study drug masking was by two consecutive nebulisations (each either ALX-0171 or placebo) depending on assigned treatment group. The primary outcome was to evaluate time for the RSV viral load to drop to below quantifiable limit, measured by plaque assay on mid-turbinate nasal swabs. Safety, clinical efficacy, pharmacokinetics, viral load by RT-qPCR, and immunogenicity were secondary outcomes. Analysis, including of the primary outcome, was by modified intention to treat (participants receiving at least one dose of study drug as assigned), and safety was assessed in all children who received at least one administration of study drug, as treated. This trial is registered with EudraCT, 2016-001651-49.
Between Jan 10, 2017, and April 26, 2018, 175 children (median age 4·8 months IQR 2·0-10·8), received at least one dose of study drug (45 received 3 mg/kg of ALX-0171, 43 received 6 mg/kg of ALX-0171, 45 received 9 mg/kg of ALX-0171, and 42 received placebo; the modified intention-to-treat population) commencing at a mean 3·3 days (SD 1·1) from symptom onset. Median time for the viral load to drop to below quantifiable limit on plaque assay was significantly faster for the 3 mg/kg group (median 14·2 h IQR 5·0-28·0), 6 mg/kg group (5·1 h 4·7-28·5), and 9 mg/kg group (5·1 h 4·6-5·9) than the placebo group (46·1 h 25·2-116·7; hazard ratio HR all ALX-0171 groups vs placebo 2·6 1·7-3·9; p<0·0001). Median time for the viral load to drop below quantification limit with RT-qPCR was 95·9 h (IQR 26·7 to not estimable) for the placebo group (n=35) versus 49·4 h (25·1 to 351·4) for all ALX-0171 groups (n=118). Clinical outcomes were not improved by ALX-0171 compared with placebo, with no difference in time to clinical response (oxygen saturation >92% for 4 h in room air and adequate oral feeding) in ALX-0171 groups and the placebo group (median 43·8 h IQR 21·7-68·5 vs 47·9 h 22·5-76·4; HR 1·1 95% CI 0·8-1·6) or change in the global severity score from baseline to 5 h post-dose on day 2 (-4 IQR -6 to -2 vs -4 -6 to -1; difference in least-squares mean -0·45 95% CI -1·39 to 0·49). Serum concentrations of ALX-0171 on day 2 exceeded the concentration estimated to give full RSV neutralisation in the lung at 6 mg/kg and 9 mg/kg doses. Treatment-emergent antidrug antibodies were detected at day 14 in 46 (34%) of 135 patients who received ALX-0171 and ten (26%) of 39 patients who received placebo. Serious adverse events were reported in five (13%) of 40 children in the placebo group and ten (7%) of 135 children in all ALX-0171 groups, leading to study drug discontinuation in three children (two in the 3 mg/kg group and one in the 6 mg/kg group). 13 of 15 serious adverse events (three of four in the 3 mg/kg group, two of three in the 6 mg/kg group, three of three in the 9 mg/kg group, and five of five in the placebo group) were related to worsening respiratory status, and none were considered to be related to the study drug.
Antivirals against RSV might be unable to improve clinical course once RSV lower respiratory tract infection is established. Future studies of RSV antivirals should focus on earlier intervention and more precise measurement of objective outcomes before the onset of significant lower respiratory tract inflammation.
Ablynx, a Sanofi Company.
Sipnja je jedan od najčešćih respiratornih simptoma u predškolskoj dobi. U većine djece sipnja je vezana isključivo za virusne infek cije
gornjih dišnih putova i s vremenom je prolazna, no trećina ...djece s ponavljajućom sipnjom ima postavljenu dijagnozu astme u
školskoj dobi. Prema smjernicama stručnih društava ponavljajuća sipnja se u predškolskoj dobi najčešće klasifi cira u fenotipove,
ovisno o učestalosti simptoma i njihovoj povezanosti s određenim okidačima. Upalna patogeneza fenotipova sipnje u predškolskoj
dobi zasad nije poznata, ali vjerojatno je riječ o različitim upalnim mehanizmima. Većina djece s ponavljajućom sipnjom u predškolskoj
dobi može se liječiti samo bronhodilatatorima. Prema smjernicama Europskog respiratornog društva protuupalnu terapiju
treba započeti u bolesnika koji imaju učestale simptome i tešku kliničku sliku. Mjerenje objektivnih parametara kao što su plućna
funkcija i hiperreaktivnost dišnih putova otežano je zbog nesuradnje, tako da je uvođenje terapije i dobar klinički odgovor vjerojatno
najpouzdaniji put za dijagnozu astme. U ovom trenutku ne postoje strategije liječenja koje bi modifi cirale tijek bolesti i spriječile
razvoj perzistentne sipnje odnosno astme.
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