The COVID-19 outbreak has rapidly expanded to a global pandemic; however, our knowledge is limited with regards to the protective factors against this infection. The aim of this systematic literature ...review and meta-analysis was to evaluate the impact of vitamin D supplementation on COVID-19 related outcomes. A systematic search of relevant papers published until January 2022 was conducted to identify randomized controlled trials (RCTs) and non-randomized studies of intervention (NRISs). The primary outcomes included the risk of COVID-19 infection (primary prevention studies on uninfected individuals), hospital admission (secondary prevention studies on mild COVID-19 cases), and ICU admission and mortality rate (tertiary prevention studies on hospitalized COVID-19 patients). We identified five studies (one RCT, four NRISs) on primary prevention, with five (two RCTs, three NRISs) on secondary prevention, and 13 (six RCTs, seven NRISs) on tertiary prevention. Pooled analysis showed no significant effect on the risk of COVID-19 infection. No meta-analysis was possible on hospitalization risk due to paucity of data. Vitamin D supplementation was significantly associated with a reduced risk of ICU admission (RR = 0.35, 95% CI: 0.20, 0.62) and mortality (RR = 0.46, 95% CI: 0.30, 0.70). Vitamin D supplementation had no significant impact on the risk of COVID-19 infection, whereas it showed protective effects against mortality and ICU admission in COVID-19 patients.
Summary Preschool children (ie, those aged 5 years or younger) with wheeze consume a disproportionately high amount of health-care resources compared with older children and adults with wheeze or ...asthma, representing a diagnostic challenge. Although several phenotype classifications have been described, none have been validated to identify individuals responding to specific therapeutic approaches. Several risk factors related to genetic, prenatal, and postnatal environment are associated with preschool wheezing. Findings from several cohort studies have shown that preschool children with wheeze have deficits in lung function at 6 years of age that persisted until early and middle adulthood, suggesting increased susceptibility in the first years of life that might lead to persistent sequelae. Daily inhaled corticosteroids seem to be the most effective therapy for recurrent wheezing in trials of children with interim symptoms or atopy; intermittent high-dose inhaled corticosteroids are effective in moderate-to-severe viral-induced wheezing without interim symptoms. The role of leukotriene receptor antagonist is less clear. Interventions to modify the short-term and long-term outcomes of preschool wheeze should be a research priority.
Home blood self-collection devices can enable remote monitoring, but their implementation requires validation. Our objectives were to explore (i) the impact of sampling sites and topical analgesia on ...capillary blood volume and pain perception and (ii) the safety, acceptability, and failure of capillary self-collection among adults and children using the Tasso-SST device.
We conducted a two-phase study. The investigational phase consisted of two on-site cross-sectional studies in healthy adult participants (≥ 12 years) and children (1-17 years) with their accompanying parent. Adults received 4 capillary samplings, where puncture sites and topical analgesia were randomized in a factorial design, and a venipuncture; children (and one parent) had one capillary sampling. The two co-primary outcomes were blood volume and pain. The implementation phase was conducted in two multicentre trials in participants choosing remote visits; blood volume, collection failure, adverse events, and satisfaction were documented.
In the investigational phase, 90 participants and 9 children with 7 parents were enrolled; 15 adults and 2 preschoolers participated in the implementation phase. In the adult investigational study, the device collected a median (25%, 75%) of 450 (250, 550) μl of blood with no significant difference between the puncture site, topical analgesia, and its interaction. Using topical analgesia reduced pain perception by 0.61 (95% CI: 0.97, 0.24; P <0.01) points on the 11-point scale; the pain reduction varied by puncture site, with the lower back showing the most significant decrease. Overall, combining all studies and phases, the median volume collected was 425 (250, 500) μl, and the device failure rate was 4.4%; minor adverse effects were reported in 8.9% of the participants, all were willing to use the device again.
Capillary blood self-collection, yielding slightly less than 500 μl, proves to be a safe and relatively painless method for adults and children, with high satisfaction and low failure rates. The puncture site and topical analgesia do not affect blood volume, but topical analgesia on the lower back could reduce pain.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Anti‐leukotrienes (5‐lipoxygenase inhibitors and leukotriene receptors antagonists) serve as alternative monotherapy to inhaled corticosteroids (ICS) in the management of recurrent and/or ...chronic asthma in adults and children.
Objectives
To determine the safety and efficacy of anti‐leukotrienes compared to inhaled corticosteroids as monotherapy in adults and children with asthma and to provide better insight into the influence of patient and treatment characteristics on the magnitude of effects.
Search methods
We searched MEDLINE (1966 to Dec 2010), EMBASE (1980 to Dec 2010), CINAHL (1982 to Dec 2010), the Cochrane Airways Group trials register, and the Cochrane Central Register of Controlled Trials (Dec 2010), books, and reference lists of review articles and trials. We contacted colleagues and the international headquarters of anti‐leukotrienes producers.
Selection criteria
We included randomised trials that compared anti‐leukotrienes with inhaled corticosteroids as monotherapy for a minimum period of four weeks in patients with asthma aged two years and older.
Data collection and analysis
Two review authors independently assessed the methodological quality of trials and extracted data. The primary outcome was the number of patients with at least one exacerbation requiring systemic corticosteroids. Secondary outcomes included patients with at least one exacerbation requiring hospital admission, lung function tests, indices of chronic asthma control, adverse effects, withdrawal rates and biological inflammatory markers.
Main results
Sixty‐five trials met the inclusion criteria for this review. Fifty‐six trials (19 paediatric trials) contributed data (representing total of 10,005 adults and 3,333 children); 21 trials were of high methodological quality; 44 were published in full‐text. All trials pertained to patients with mild or moderate persistent asthma. Trial durations varied from four to 52 weeks. The median dose of inhaled corticosteroids was quite homogeneous at 200 µg/day of microfine hydrofluoroalkane‐propelled beclomethasone or equivalent (HFA‐BDP eq). Patients treated with anti‐leukotrienes were more likely to suffer an exacerbation requiring systemic corticosteroids (N = 6077 participants; risk ratio (RR) 1.51, 95% confidence interval (CI) 1.17, 1.96). For every 28 (95% CI 15 to 82) patients treated with anti‐leukotrienes instead of inhaled corticosteroids, there was one additional patient with an exacerbation requiring rescue systemic corticosteroids. The magnitude of effect was significantly greater in patients with moderate compared with those with mild airway obstruction (RR 2.03, 95% CI 1.41, 2.91 versus RR 1.25, 95% CI 0.97, 1.61), but was not significantly influenced by age group (children representing 23% of the weight versus adults), anti‐leukotriene used, duration of intervention, methodological quality, and funding source. Significant group differences favouring inhaled corticosteroids were noted in most secondary outcomes including patients with at least one exacerbation requiring hospital admission (N = 2715 participants; RR 3.33; 95% CI 1.02 to 10.94), the change from baseline FEV1 (N = 7128 participants; mean group difference (MD) 110 mL, 95% CI 140 to 80) as well as other lung function parameters, asthma symptoms, nocturnal awakenings, rescue medication use, symptom‐free days, the quality of life, parents' and physicians' satisfaction. Anti‐leukotriene therapy was associated with increased risk of withdrawals due to poor asthma control (N = 7669 participants; RR 2.56; 95% CI 2.01 to 3.27). For every thirty one (95% CI 22 to 47) patients treated with anti‐leukotrienes instead of inhaled corticosteroids, there was one additional withdrawal due to poor control. Risk of side effects was not significantly different between both groups.
Authors' conclusions
As monotherapy, inhaled corticosteroids display superior efficacy to anti‐leukotrienes in adults and children with persistent asthma; the superiority is particularly marked in patients with moderate airway obstruction. On the basis of efficacy, the results support the current guidelines' recommendation that inhaled corticosteroids remain the preferred monotherapy.
Background
There are several treatment options for managing acute asthma exacerbations (sustained worsening of symptoms that do not subside with regular treatment and require a change in management). ...Guidelines advocate the use of inhaled short acting beta2‐agonists (SABAs) in children experiencing an asthma exacerbation. Anticholinergic agents, such as ipratropium bromide and atropine sulfate, have a slower onset of action and weaker bronchodilating effect, but may specifically relieve cholinergic bronchomotor tone and decrease mucosal edema and secretions. Therefore, the combination of inhaled anticholinergics with SABAs may yield enhanced and prolonged bronchodilation.
Objectives
To determine whether the addition of inhaled anticholinergics to SABAs provides clinical improvement and affects the incidence of adverse effects in children with acute asthma exacerbations.
Search methods
We searched MEDLINE (1966 to April 2000), EMBASE (1980 to April 2000), CINAHL (1982 to April 2000) and reference lists of studies of previous versions of this review. We also contacted drug manufacturers and trialists. For the 2012 review update, we undertook an 'all years' search of the Cochrane Airways Group's register on the 18 April 2012.
Selection criteria
Randomized parallel trials comparing the combination of inhaled anticholinergics and SABAs with SABAs alone in children (aged 18 months to 18 years) with an acute asthma exacerbation.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data. We used the GRADE rating system to assess the quality of evidence for our primary outcome (hospital admission).
Main results
Twenty trials met the review eligibility criteria, generated 24 study comparisons and comprised 2697 randomised children aged one to 18 years, presenting predominantly with moderate or severe exacerbations. Most studies involved both preschool‐aged children and school‐aged children; three studies also included a small proportion of infants less than 18 months of age. Nine trials (45%) were at a low risk of bias. Most trials used a fixed‐dose protocol of three doses of 250 mcg or two doses of 500 mcg of nebulized ipratropium bromide in combination with a SABA over 30 to 90 minutes while three trials used a single dose and two used a flexible‐dose protocol according to the need for SABA.
The addition of an anticholinergic to a SABA significantly reduced the risk of hospital admission (risk ratio (RR) 0.73; 95% confidence interval (CI) 0.63 to 0.85; 15 studies, 2497 children, high‐quality evidence). In the group receiving only SABAs, 23 out of 100 children with acute asthma were admitted to hospital compared with 17 (95% CI 15 to 20) out of 100 children treated with SABAs plus anticholinergics. This represents an overall number needed to treat for an additional beneficial outcome (NNTB) of 16 (95% CI 12 to 29).
Trends towards a greater effect with increased treatment intensity and with increased asthma severity were observed, but did not reach statistical significance. There was no effect modification due to concomitant use of oral corticosteroids and the effect of age could not be explored. However, exclusion of the one trial that included infants (< 18 months) and contributed data to the main outcome, did not affect the results. Statistically significant group differences favoring anticholinergic use were observed for lung function, clinical score at 120 minutes, oxygen saturation at 60 minutes, and the need for repeat use of bronchodilators prior to discharge from the emergency department. No significant group difference was seen in relapse rates.
Fewer children treated with anticholinergics plus SABA reported nausea and tremor compared with SABA alone; no significant group difference was observed for vomiting.
Authors' conclusions
Children with an asthma exacerbation experience a lower risk of admission to hospital if they are treated with the combination of inhaled SABAs plus anticholinergic versus SABA alone. They also experience a greater improvement in lung function and less risk of nausea and tremor. Within this group, the findings suggested, but did not prove, the possibility of an effect modification, where intensity of anticholinergic treatment and asthma severity, could be associated with greater benefit.
Further research is required to identify the characteristics of children that may benefit from anticholinergic use (e.g. age and asthma severity including mild exacerbation and impending respiratory failure) and the treatment modalities (dose, intensity, and duration) associated with most benefit from anticholinergic use better.
While the association between vitamin D and several inflammatory biomarkers in asthma patients has been extensively reported, it remains unclear whether supplementation modifies these biomarkers. ...This review aims to evaluate the impact of vitamin D supplementation on inflammatory biomarkers measured
in individuals with asthma.
We conducted a systematic review of randomized controlled trials (RCTs) published until November 2022 in six electronic databases evaluating the impact of vitamin D supplementation (any dose, form, administration route, frequency, or duration) compared to placebo in children or adults. The two co-primary outcomes were serum IgE and blood eosinophils reported at the endpoint. Secondary outcomes included other markers of type 2 inflammation (e.g., sputum eosinophils, fractional exhaled nitric oxide, etc.), anti-inflammatory biomarkers (e.g., interleukin (IL)-10, etc.), markers of non-type 2 inflammation (e.g., high-sensitivity C-reactive protein, etc.), and non-specific biomarkers (e.g., macrophages, etc.). Data were aggregated using fixed or random effect models.
Thirteen RCTs (5 in adults, 5 in pediatric patients, and 3 in mixed age groups) testing doses of vitamin D supplementation ranging from 800 to 400,000 IU over periods of 6 weeks to 12 months were included. Eight studies provided data on serum IgE and four on blood eosinophils. As secondary outcomes, three studies reported on sputum eosinophils, four on FeNO, five on serum IL-10, and two on airway IL-10. Compared to placebo, vitamin D supplementation had no significant effect on serum IgE (Mean difference MD 95% CI: 0.06 -0.13, 0.26 IU/mL), blood eosinophils (MD 95% CI: - 0.02 -0.11, 0.07 10
/μL), or FeNO (MD 95% CI: -4.10 -10.95, 2.75 ppb) at the endpoint. However, the vitamin D supplementation group showed higher serum IL-10 levels compared to placebo (MD 95% CI: 18.85 1.11, 36.59 pg/ml) at the endpoint. Although data could not be aggregated, narrative synthesis suggested no significant effect of supplementation on sputum eosinophils and IL-10 in both sputum and exhaled breath condensate, at the endpoint.
Vitamin D supplementation in individuals with asthma was not associated with lower inflammatory biomarkers related to type 2 inflammation. However, it was significantly associated with higher serum IL-10 compared to placebo.
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022365666.
: media-1vid110.1542/5771275574001PEDS-VA_2017-4105
OBJECTIVES: Respiratory pathogens commonly trigger pediatric asthma exacerbations, but their impact on severity and treatment response remains ...unclear.
We performed a secondary analysis of the Determinants of Oral Corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY) study, a prospective cohort study of children (aged 1-17 years) presenting to the emergency department with moderate or severe exacerbations. Nasopharyngeal specimens were analyzed by RT-PCR for 27 respiratory pathogens. We investigated the association between pathogens and both exacerbation severity (assessed with the Pediatric Respiratory Assessment Measure) and treatment failure (hospital admission, emergency department stay >8 hours, or relapse) of a standardized severity-specific treatment. Logistic multivariate regressions were used to estimate average marginal effects (absolute risks and risk differences RD).
Of 958 participants, 61.7% were positive for ≥1 pathogen (rhinovirus was the most prevalent 29.4%) and 16.9% experienced treatment failure. The presence of any pathogen was not associated with higher baseline severity but with a higher risk of treatment failure (20.7% vs 12.5%; RD = 8.2% 95% confidence interval: 3.3% to 13.1%) compared to the absence of a pathogen. Nonrhinovirus pathogens were associated with an increased absolute risk (RD) of treatment failure by 13.1% (95% confidence interval: 6.4% to 19.8%), specifically, by 8.8% for respiratory syncytial virus, 24.9% for influenza, and 34.1% for parainfluenza.
Although respiratory pathogens were not associated with higher severity on presentation, they were associated with increased treatment failure risk, particularly in the presence of respiratory syncytial virus, influenza, and parainfluenza. This supports influenza prevention in asthmatic children, consideration of pathogen identification on presentation, and exploration of treatment intensification for infected patients at higher risk of treatment failure.
Background
Long‐acting beta2‐agonists (LABA) in combination with inhaled corticosteroids (ICS) are increasingly prescribed for children with asthma.
Objectives
To assess the safety and efficacy of ...adding a LABA to an ICS in children and adolescents with asthma. To determine whether the benefit of LABA was influenced by baseline severity of airway obstruction, the dose of ICS to which it was added or with which it was compared, the type of LABA used, the number of devices used to deliver combination therapy and trial duration.
Search methods
We searched the Cochrane Airways Group Asthma Trials Register until January 2015.
Selection criteria
We included randomised controlled trials testing the combination of LABA and ICS versus the same, or an increased, dose of ICS for at least four weeks in children and adolescents with asthma. The main outcome was the rate of exacerbations requiring rescue oral steroids. Secondary outcomes included markers of exacerbation, pulmonary function, symptoms, quality of life, adverse events and withdrawals.
Data collection and analysis
Two review authors assessed studies independently for methodological quality and extracted data. We obtained confirmation from trialists when possible.
Main results
We included in this review a total of 33 trials representing 39 control‐intervention comparisons and randomly assigning 6381 children. Most participants were inadequately controlled on their current ICS dose. We assessed the addition of LABA to ICS (1) versus the same dose of ICS, and (2) versus an increased dose of ICS.
LABA added to ICS was compared with the same dose of ICS in 28 studies. Mean age of participants was 11 years, and males accounted for 59% of the study population. Mean forced expiratory volume in one second (FEV1) at baseline was ≥ 80% of predicted in 18 studies, 61% to 79% of predicted in six studies and unreported in the remaining studies. Participants were inadequately controlled before randomisation in all but four studies.
There was no significant group difference in exacerbations requiring oral steroids (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.70 to 1.28, 12 studies, 1669 children; moderate‐quality evidence) with addition of LABA to ICS compared with ICS alone. There was no statistically significant group difference in hospital admissions (RR 1.74, 95% CI 0.90 to 3.36, seven studies, 1292 children; moderate‐quality evidence)nor in serious adverse events (RR 1.17, 95% CI 0.75 to 1.85, 17 studies, N = 4021; moderate‐quality evidence). Withdrawals occurred significantly less frequently with the addition of LABA (23 studies, 471 children, RR 0.80, 95% CI 0.67 to 0.94; low‐quality evidence). Compared with ICS alone, addition of LABA led to significantly greater improvement in FEV1 (nine studies, 1942 children, inverse variance (IV) 0.08 L, 95% CI 0.06 to 0.10; mean difference (MD) 2.99%, 95% CI 0.86 to 5.11, seven studies, 534 children; low‐quality evidence), morning peak expiratory flow (PEF) (16 studies, 3934 children, IV 10.20 L/min, 95% CI 8.14 to 12.26), reduction in use of daytime rescue inhalations (MD ‐0.07 puffs/d, 95% CI ‐0.11 to ‐0.02, seven studies; 1798 children) and reduction in use of nighttime rescue inhalations (MD ‐0.08 puffs/d, 95% CI ‐0.13 to ‐0.03, three studies, 672 children). No significant group difference was noted in exercise‐induced % fall in FEV1, symptom‐free days, asthma symptom score, quality of life, use of reliever medication and adverse events.
A total of 11 studies assessed the addition of LABA to ICS therapy versus an increased dose of ICS with random assignment of 1628 children. Mean age of participants was 10 years, and 64% were male. Baseline mean FEV1 was ≥ 80% of predicted. All trials enrolled participants who were inadequately controlled on a baseline inhaled steroid dose equivalent to 400 µg/d of beclomethasone equivalent or less.
There was no significant group differences in risk of exacerbation requiring oral steroids with the combination of LABA and ICS versus a double dose of ICS (RR 1.69, 95% CI 0.85 to 3.32, three studies, 581 children; moderate‐quality evidence) nor in risk of hospital admission (RR 1.90, 95% CI 0.65 to 5.54, four studies, 1008 children; moderate‐quality evidence).
No statistical significant group difference was noted in serious adverse events (RR 1.54, 95% CI 0.81 to 2.94, seven studies, N = 1343; moderate‐quality evidence) and no statistically significant differences in overall risk of all‐cause withdrawals (RR 0.96, 95% CI 0.67 to 1.37, eight studies, 1491 children; moderate‐quality evidence). Compared with double the dose of ICS, use of LABA was associated with significantly greater improvement in morning PEF (MD 8.73 L/min, 95% CI 5.15 to 12.31, five studies, 1283 children; moderate‐quality evidence), but data were insufficient to aggregate on other markers of asthma symptoms, rescue medication use and nighttime awakening. There was no group difference in risk of overall adverse effects, A significant group difference was observed in linear growth over 12 months, clearly indicating lower growth velocity in the higher ICS dose group (two studies: MD 1.21 cm/y, 95% CI 0.72 to 1.70).
Authors' conclusions
In children with persistent asthma, the addition of LABA to ICS was not associated with a significant reduction in the rate of exacerbations requiring systemic steroids, but it was superior for improving lung function compared with the same or higher doses of ICS. No differences in adverse effects were apparent, with the exception of greater growth with the use of ICS and LABA compared with a higher ICS dose. The trend towards increased risk of hospital admission with LABA, irrespective of the dose of ICS, is a matter of concern and requires further monitoring.
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