Iwona Stelmach

Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data

Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect. Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials. Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015. Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome. Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality. Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit. Systematic review registration PROSPERO CRD42014013953.

A randomized, double‐blind trial of the effect of glucocorticoid, antileukotriene and bβ‐agonist treatment on IL‐10 serum levels in children with asthma

Background Levels of an immunoregulatory and anti‐inflammatory cytokine IL‐10 are reduced in asthmatic airways, potentially contributing to more intense inflammation. Triamcinolone has anti‐inflammatory properties and the anti‐inflammatory effects of montelukast and formoterol have been discussed.

Efficacy and safety of high-doses sublingual immunotherapy in ultra-rush scheme in children allergic to grass pollen

Background Although sublingual immunotherapy (SLIT) has been used with increasing frequency, the data on the efficacy of SLIT in pediatric asthma are limited.

The prevalence of mouse allergen in inner‐city homes

Mouse allergen has not been studied in detail in the general population. It is common for patients from inner‐city environments to report significant mouse infestation in their homes and neighborhoods. The aim of this study was to determine the prevalence of mouse allergen in the homes of inner‐city children with asthma in relation to the demographic features of these children and their specific housing characteristics. Seventy‐eight dust samples from 39 inner‐city homes of Lodz, Poland, were analyzed for mouse allergen. Skin‐prick tests (SPTs) to mouse allergen were performed in all patients. In addition, data regarding the demographics and housing of the subjects were related to the mouse allergen levels. Mouse allergen was detected in 22 of 78 dust samples (28%), and in 18 of 39 homes (46%), including 13 kitchen (33%) and nine bedroom (23%) samples. Mouse allergen levels did not correlate between different rooms in the same home. The levels detected ranged from 0.09 to 2.34 µg/g of dust. The highest levels were found in kitchens, with median levels of 0.2 µg/g, 95% confidence interval (CI): 0.12–0.85 (range: 0.1–2.34 µg/g); in bedrooms the mean levels were 0.23 µg/g, 95% CI: 0.1–0.97 (range: 0.09–1.62 µg/g). Eleven of 18 children with detectable mouse allergen in house dust, and three of 21 without detectable mouse allergen in house dust, had a positive SPT to mouse allergen. On home inspection, 18% of the homes had evidence of mice in one or two rooms and had higher levels of mouse allergen (p < 0.01). None of the other subject or housing variables evaluated were associated with higher mouse allergen levels. In Polish children, mouse allergen is an important factor of sensitivity and should be recognized in the diagnosis of allergic diseases as well as in allergen‐reduction programmes.

Comparative effect of pre‐coseasonal and continuous grass sublingual immunotherapy in children

To cite this article: Stelmach I, Kaluzińska‐Parzyszek I, Jerzynska J, Stelmach P, Stelmach W, Majak P. Comparative effect of pre‐coseasonal and continuous grass sublingual immunotherapy in children. Allergy 2012; 67: 312–320.

The effect of oral steroids with and without vitamin D3 on early efficacy of immunotherapy in asthmatic children

Background The possibility of additional strategies to enhance the effectiveness of specific immunotherapy (SIT) is highly attractive.

Combined occurrence of filaggrin mutations and IL‐10 or IL‐13 polymorphisms predisposes to atopic dermatitis

Background:  Although filaggrin mutations are presently believed to play a key role in the development of atopic dermatitis (AD), obviously also immunological factors involved in acquired immune response are important for the development of allergic inflammation.

Effects of montelukast treatment on clinical and inflammatory variables in patients with cystic fibrosis

BACKGROUND In cystic fibrosis (CF), the inflammatory process contributes to progressive lung tissue damage. Cysteinyl leukotrienes have been found in the sputum of patients with CF at high concentrations sufficient to cause potent biological effects. OBJECTIVE To evaluate the effect of anti-inflammatory treatment with montelukast sodium in patients with CF. METHODS Twenty-six patients aged 6 to 18 years were recruited to this 20-week, randomized, double-blind, placebo-controlled, crossover trial. Patients received montelukast or placebo for 8 weeks in addition to their regular CF treatment. Before and after treatment, findings from spirometry, whole-body plethysmography, and the clinical wheezing and cough scales were evaluated. At the same time, serum and sputum samples were obtained for the measurement of eosinophil cationic protein, interleukin 10 (IL-10), IL-8, and myeloperoxidase levels. RESULTS Twenty-three patients completed the study. Compared with placebo use, montelukast treatment significantly improved forced expiratory volume in I second, peak expiratory flow, and forced expiratory flow between 25% and 75% and significantly decreased cough and wheezing scale scores (P < .001 for all). There were no significant changes in vital capacity, thoracic gas volume, airway resistance, and residual volume after treatment. Compared with placebo use, montelukast treatment decreased serum and sputum levels of eosinophil cationic protein and IL-8, decreased sputum levels of myeloperoxidase, and increased serum and sputum levels of IL-10 (P < .001 for all). CONCLUSIONS Montelukast may have measurable anti-inflammatory properties in patients with CF.

Comparison of the long-term efficacy of 3- and 5-year house dust mite allergen immunotherapy

BACKGROUND The recommended duration of specific immunotherapy (SIT) treatment relies on empiric data and is not well documented. OBJECTIVE To detect possible differences in the long-term effectiveness between 3 and 5 years of house dust mite (HDM) SIT in asthmatic children. METHODS We performed a 3-year natural history study of 90 asthmatic children who were sensitive only to HDM. Three groups were recruited: 30 who had completed 3 years of HDM SIT (SIT3), 30 who had completed 5 years of HDM SIT (SIT5), and 30 who had an indication for HDM SIT but whose parents refused HDM SIT. Patients attended an enrollment visit in 2007, after SIT discontinuation, and 3 annual follow-up visits at the clinic. The long-term effectiveness of HDM SIT was primarily assessed via analysis of the reduction in required inhaled corticosteroid dose, forced expiratory volume in 1 second, and asthma remission. RESULTS A total of 84 children completed the study. Both SIT durations produced excellent results; asthma remission in both SIT3 (50%) and SIT5 (54%) groups was significantly higher when compared with control (3.3%). The minimal controlling inhaled corticosteroid dose reduction in SIT5 group (median, 75%) was significantly higher compared with the SIT3 group (median, 50%) after immunotherapy discontinuation; after 3 years without SIT, no differences were found between the SIT5 and SIT3 groups (median, 100% and 94%, respectively). We observed a slightly higher increase in forced expiratory volume in 1 second in the SIT5 group compared with the SIT3 group. CONCLUSION Three years of SIT is an adequate duration for the treatment of childhood asthma associated with HDM allergy because 2 further years of SIT added no clinical benefit.

Exercise-Induced Bronchoconstriction in Asthmatic Children

The aim of this article is to critically review the efficacy and safety data from randomized controlled trials (RCTs) using inhaled corticosteroids (ICSs), long- or short-acting β2-adrenoceptor agonists (LABAs, SABAs), parasympatholytics and oral leukotriene receptor antagonists in the management of exercise-induced bronchoconstriction (EIB) in children with persistent asthma (EIA).The studies with sufficient information on patient characteristics and outcomes were chosen using a MEDLINE search. Results from the individual searches were combined and repeated. Studies were also found by reviewing the reference lists of the articles not included in this review. Studies focusing solely on individuals with asthma and other allergic co-morbidities (i.e. a degree of bronchial reversibility) were considered in this review. To make the paper evidence-based, the design and the quality of different studies were assessed employing the Sign criteria (evidence level [EL] and grades of recommendation [GR]). No additional statistical analyses were performed. Most of studies included paediatric patients with underlying EIA.We need to distinguish children with recurrent asthma symptoms in whom EIB is also present (patients with EIA) from asthmatic subjects whose symptoms appear only as a result of exercise (patients with EIB). Further controller treatment is indicated in patients with EIA and further reliever treatment in patients with EIB. ICSs are the first-choice controller drugs for EIA in children with persistent asthma (Sign grade of recommendation [GR]:A). In children with EIA without complete control with ICSs, SABAs (GR:A), leukotriene receptor antagonists (LTRAs) [GR:A] or LABAs (GR:A) may be added to gain control. Treatment with relievers such as SABAs (GR:A), parasympatholytics (GR:B) or, eventually, LABAs (GR:A), administered 10–15 minutes before exercise is the most preferable method of preventing EIB symptoms in children; however, not as monotherapy in children with EIA.The disadvantages and controversy relating to inhaled β2-adrenoceptor agonist use lie in the development of tolerance to their effect when they are used on a regular basis, and the possibility of a resulting underuse of ICSs in patients with EIA. Researchers and guidelines recommend that if any patient requires treatment with a β2-adrenoceptor agonist more than twice weekly, a low dose of ICSs should be administered. Inhaled parasympatholytics may be effective as preventive relievers in some children with EIB or EIA, especially among those with increased vagal activity. LTRAs have a well balanced efficacy-safety profile in preventing the occurrence of EIB symptoms in children. Compared with LABAs, LTRAs produce persistent attenuation of EIB and possess an additional effect with rescue SABA therapy in persistent asthmatic patients with EIA. A disadvantage of LTRAs is a non-response phenomenon. There are still insufficient data on the efficacy-safety profiles of ICS/LABA combination drugs in the treatment of EIA in children to recommend this treatment without caution. Safety profiles of inhaled SABAs, anticholinergics and montelukast in approved dosages seem sufficient enough to recommend use of these drugs in the prevention of EIB symptoms in children. Many researchers agree that treatment of EIA in children should always be individualized.