Negative Asthma Predictive Index Research Articles

Рівень забезпеченості вітаміном D та особливості продукції IFN-γ і IL-4 у дітей раннього віку з повторним бронхообструктивним синдромом

Актуальність. Бронхообструктивний синдром (БОС), зокрема його повторний перебіг у дітей раннього віку, є актуальною проблемою сучасної педіатрії. Обтяжений алергологічний анамнез, прояви атопії традиційно розглядаються як фактори ризику повторних епізодів БОС, які, однак, присутні не в усіх випадках. Останнім часом обговорюється можлива роль вітаміну D (VD) у формуванні схильності до повторних епізодів БОС з огляду на його протиінфекційну дію, що забезпечується шляхом активації імунних механізмів. Мета: вивчення рівня забезпеченості VD і особливостей продукції інтерферону гамма (INF-g) та інтерлейкіну-4 (IL-4) у сироватці крові в дітей раннього віку з повторними епізодами БОС. Матеріали та методи. Обстежені 120 дітей віком від 6 місяців до 3 років з клінічним діагнозом «гострий обструктивний бронхіт» (J20), які були розподілені на дві групи (I група — 60 дітей з епізодичним БОС, II група — 60 дітей із повторним БОС). Групу контролю становили 30 клінічно здорових дітей віком від 6 місяців до 3 років. Усім хворим проводили оцінку анамнестичних даних, у тому числі рівня інсоляції, ступеня тяжкості БОС за 12-бальною оціночною шкалою, загальне клінічне обстеження, пульс­оксиметрію, розраховували прогностичний індекс бронхіальної астми (API). Лабораторні дослідження включали визначення на 2–3-й день захворювання концентрації 25-гідроксивітаміну D (25(OH)D) у сироватці крові електрохемілюмінесцентним методом на аналізаторі Cobas e411 (серійний номер 1041-24, виробник Roche Diagnostics GmbH, Німеччина), сироваткових концентрацій IFN-g, IL-4 методом імуноферментного аналізу за допомогою наборів «ІФА-Бест» (виробник «Вектор-Бест», Російська Федерація) та загального кальцію (Са) за загальноприйнятою методикою. При аналізі отриманих даних використовували непараметричні статистичні критерії. Різниця між показниками, що порівнювались, вважалась вірогідною при р < 0,05. Результати. Більшість пацієнтів із повторним перебігом захворювання (56,7 %) мали 4 епізоди БОС за останні 12 місяців. Аналіз анамнестичних показників, у тому числі алергологічного анамнезу, не виявив суттєвих відмінностей між групами (p > 0,05). У 78,3 % пацієнтів II групи був негативний API. Тяжкий перебіг БОС удвічі частіше реєструвався серед дітей II групи порівняно з I групою (23,3 і 10,0 % відповідно, c2 = 4,50, р = 0,034). Середній вміст 25(OH)D у сироватці крові у дітей I групи становив 33,0 (28,19; 41,97) нг/мл; II групи — 13,68 (7,96; 19,51) нг/мл (p < 0,001). Рівень забезпеченості VD у 75 % дітей II групи відповідав критеріям дефіциту, тоді як у I групі даний показник становив 6,6 % (c2 = 57,98, p < 0,001). Виявлено обернену залежність між рівнем VD і частотою (r = –0,27, р = 0,002), та тяжкістю перебігу БОС (r = — 0,24, р = 0,008). Рівень загального Са в сироватці крові в обох групах був у межах нормальних величин. Середній рівень IFN-g у дітей І групи становив 22,69 (8,98; 41,44) пг/мл та ІІ групи — 21,08 (8,57; 37,03) пг/мл, обидва показники були вищими, ніж у групі контролю, — 12,18 (5,31; 12,92) пг/мл (p = 0,016 для обох показників). Ми виявили, що досліджувані групи відрізнялись між собою за рівнем саплементації VD, показник якого становив 60 % у I групі та 5 % — у дітей II групи (p < 0,001). Середній вміст IL-4 у сироватці крові в дітей I групи був вірогідно вищим порівняно з відповідними показниками II групи та групи контролю (р = 0,012 за U-критерієм Манна — Уїтні для обох показників). Виявлено обернений кореляційний зв’язок між частотою БОС і вмістом IFN-g у крові в дітей I групи (r = –0,45, р < 0,001) та між ступенем тяжкості БОС і сироватковою концентрацією IL-4 у дітей II групи (r = –0,28, р = 0,030). У пацієнтів із повторним БОС також був виявлений прямий кореляційний зв’язок між вмістом IL-4 та IFN-g (r = 0,41, р < 0,001). Ніяких кореляцій між VD та імунологічними показниками ми не виявили. Висновки. БОС у дітей раннього віку переважно має вірусну етіологію. Тяжкий перебіг захворювання частіше зустрічається в дітей із повторними епізодами БОС, для переважної більшості яких характерний негативний прогностичний індекс бронхіальної астми. У 3/4 пацієнтів із повторним БОС рівень забезпеченості VD знаходиться в межах дефіциту. VD обернено корелює з тяжкістю й частотою епізодів БОС. На рівень забезпеченості вітаміном D у дітей раннього віку найбільше впливає рівень його саплементації. Перебіг БОС у дітей раннього віку супроводжується підвищенням рівня IFN-g у сироватці крові в гострий період захворювання незалежно від частоти епізодів БОС в анамнезі. За вмістом IL-4 у сироватці крові досліджувані групи не відрізняються між собою, при цьому за наявності повторних епізодів даний показник прямо корелює з IFN-g. Отже, IFN-g і IL-4 суттєво не впливають на частоту та ступінь тяжкості БОС у дітей раннього віку на відміну від вітаміну D, що може розглядатися як предиктор тяжкого перебігу БОС і розвитку його повторних епізодів.

Уровень сывороточного периостина у детей с положительным и отрицатель¬ным предиктивным индексом астмы и у их здоровых сверстников

Уровень сывороточного периостина у детей с положительным и отрицатель¬ным предиктивным индексом астмы и у их здоровых сверстников

Relation between serum CC16 levels and asthma predictive index in pre-schoolers with recurrent wheezing

BackgroundLow levels of serum CC16 were reported in asthmatic adults, but the studies on children were scarce and conflicting. The aim of this study was to compare serum CC16 levels in pre-school children with recurrent wheezing assessed using an asthma predictive index (API). MethodsWe performed a case-control study based on API, with all enrolled pre-school children who had recurrent wheezing episodes (>3 episodes/last year confirmed by a physician) and had presented at one paediatric clinic in Santiago, Chile. The population was divided according to stringent API criteria into positive or negative. ResultsIn a one-year period, 60 pre-schoolers were enrolled. After excluding 12, 48 pre-schoolers remained (27 males, age range from 24 to 71 months) and completed the study; 34 were API positive and 14 were API negative. There were no significant differences in demographics between groups. The level of serum CC16 levels for pre-schoolers with a positive API and negative API were (median 9.2 [7.1–11.5] and 9.4 [5.5–10], p=0.26, respectively). The area under the curve for the serum CC16 levels to predict a positive API was 0.6, 95% CI [0.43–0.77], p=0.3. A correlation between serum CC16 levels and age was found (r=0.36 [0.07–0.59], p=0.01], but not between serum CC16 levels and peripheral eosinophils blood. ConclusionThere was no evidence that serum CC16 levels played a role in recurrent wheezing and a positive API in pre-school children. More studies are needed to confirm this finding.

Serum periostin is not related to asthma predictive index

BackgroundIn contrast to adult asthmatic patients, studies on the role of serum periostin levels in schoolchildren with asthma are still conflictive, and very few studies have been performed in pre-schoolers. The aim of this study was to compare serum periostin levels in recurrent wheezer pre-schoolers according to their asthma predictive index (API) condition. MethodsWe performed a case–control study enrolling pre-schoolers with recurrent wheezing episodes (>3 episodes confirmed by physician) presented at one paediatric clinic in Santiago, Chile. The population was divided according to stringent API criteria into positive or negative. ResultsIn a one-year period, 60 pre-schoolers were enrolled. After excluding 12 (due to not fulfilment of inclusion criteria or refusal of blood sample extraction), 48 remaining pre-schoolers (27 males, age range from 24 to 71 months) completed the study; 34 were API positive and 14 were API negative. There were no significant differences in demographics between groups. The level of serum periostin levels for pre-schoolers with positive API and negative API were (median 46.7 [25.5–83.1] and 67.5 [20.5–131.8], p=0.9, respectively). The area under the curve for the serum periostin levels for predict positive API was 0.5, 95% CI [0.29–0.70], p=0.9. No significant correlation between serum periostin levels and peripheral blood eosinophils was found. ConclusionSerum periostin levels were no significantly different between wheezer pre-schoolers with positive and negative API. More studies are needed to confirm this finding.

Airway tone dysfunction among pre-schoolers with positive asthma predictive index: A case–control study

ObjectiveTo measure lung function by impulse oscillometry (IOS) and spirometry in recurrent wheezer pre-schoolers according to their asthma predictive index (API) condition. MethodsWe performed a case–control study enrolling all pre-schoolers with recurrent wheezing episodes (>3 episodes confirmed by physician) who presented at a paediatric pulmonology clinic. The population was divided according to stringent API criteria into positive or negative. ResultsIn the nine-month period, 109 pre-schoolers were enrolled. After excluding one patient (due to lung function technique problems) 108 pre-schoolers (56 males, age range from 24 to 72 months) completed the study; 50 belong to positive API and 58 to negative API group. There were no differences in demographics between groups. More use of ICS was found in those with positive API than with negative API (62% vs. 12%, respectively, p=0.001). No differences in basal lung function and post-bronchodilator response to salbutamol (by IOS or spirometry) were found between positive and negative API pre-schoolers. However, those positive API pre-schoolers with ICS had significantly higher central basal airway resistance (RA at 20Hz) and higher post-BD response (% change in FEF25–75 and in FEV0.5) than those positive API without ICS. ConclusionRecurrent wheezer pre-schoolers with positive API and ICS used may have airway dysfunction. More studies are needed to confirm this finding.

Vitamin D Status in Infants with Two Different Wheezing Phenotypes.

To investigate vitamin D levels in patients with recurrent wheeze at early ages of childhood. In the present cross-sectional study, serum 25-hydroxy vitamin D [25 (OH)D], levels which is known as an indicator of vitamin D adequacy, was examined in infants with three or more wheezing attacks. A total of 186 infants with recurrent wheezing were included in the study along with 118 healthy control peers. The recurrent wheezing study participants were classified into two groups according to Asthma Predictive Index (API) positivity and compared to control subjects regarding their serum vitamin D status. The API negative group had the lowest mean serum 25 (OH)D level (n=121; 22.71±10.76ng/ml) followed by API positive group (n=65; 24.08±9.02ng/ml) compared to healthy group (26.24±11.88ng/ml) (p<0.05). In addition, higher vitamin D deficiency was observed in infants in API negative group (52.1%; p<0.01) and API positive group (38.5%; p<0.05) than control group (31.4%). Low levels of 25 (OH)D were detected in infants with two different phenotypes of recurrent wheeze. Vitamin D deficiency may play a role in the pathogenesis of infants with recurrent wheezing.

Serum level of vitamin D and trace elements in children with recurrent wheezing: a cross-sectional study.

BackgroundWe aimed to show the relationship between recurrence of wheezing and serum levels of vitamin D, zinc, and copper in wheezy children compared with a healthy group.MethodsIn this cross sectional study, seventy-three children with wheezing and seventy-five controls were included without a follow-up period. The clinical characteristics of the children were assessed, the asthma predictive index and temporal pattern of wheeze were determined. The serum levels of vitamin D, zinc, and copper were measured. Pearson correlation analysis was used to evaluate the relationship between homogeneously distributed variables.ResultsThirty-two of the seventy-three children (43.8%) had more than three wheezing attacks (recurrent wheezing). The Asthma Predictive Index index was positive in 26 patients (35.6%). When classified to temporal pattern of wheeze, fifty-three of the study group (72.6%) had episodic wheezing and the remainder (27.4%) was classified as multiple-trigger wheezing. We found no overall significant difference between the study and control group in terms of vitamin D and trace elements . The vitamin D and zinc levels were significantly lower and serum copper and copper/zinc ratio was significantly higher in patients with recurrent wheezing (p =0.03, p <0.01, p =0.013, p <0.01, respectively) positive Asthma Predictive Index and multiple-trigger temporal pattern of wheeze compared with patients with non- recurrent wheezing, negative Asthma Predictive Index and episodic temporal pattern of wheeze.ConclusionIt may be postulated that for the determination of asthma risk in patients with recurrent wheezing, the serum level of vitamin D, copper and zinc can be used as a routine biomarker alongside the Asthma Predictive Index and temporal pattern of wheeze.

Asociación entre el índice de predicción de asma y el óxido nítrico exhalado en niños pequeños con sibilancias recurrentes

It is difficult to make an early identification of which children with recurrent wheezing will develop asthma in the following years. The Asthma Predictive Index (API) is a questionnaire based on clinical and laboratory parameters used for this end. The measurement of fractional exhaled nitric oxide (FE NO) has been used as a marker of eosinophilic airway infammation in asthma patients. Objective. To determine the association between the Asthma Predictive Index and FE NO levels in children younger than 3 years old with recurrent wheezing. Materials and methods. Observational, cross sectional study. Children younger than 36 months old with 3 or more episodes of bronchial obstruction in the past year who were inhaled corticosteroid-naive or leukotriene receptor antagonist-naive were included. After recording clinical data, FE NO was measured by a chemiluminescence analyzer during tidal breathing (online method). Results. A total of 52 children aged 5-36 months old were included. Patients with a positive API accounted for 60% of the population and had higher levels of FE NO than those with a negative API, with a median (range) of 13.5 ppb (0.7-31) versus 5.6 ppb (0.1-20.8), respectively (p <0.01). A high FE NO (>8 ppb) was observed in 74% of children with a positive API and in 26% of those with a negative API (p <0.01). Conclusions. This study found an association between high levels of exhaled nitric oxide and a positive Asthma Predictive Index in children younger than 3 years old with recurrent wheezing.

Young Infants with Recurrent Wheezing and Positive Asthma Predictive Index Have Higher Levels of Exhaled Nitric Oxide

Objective. The aim of this post hoc analysis was to establish the relationship between FENO levels and the asthma predictive index (API) among infants with recurrent wheezing. Methods. Infants with recurrent wheezing (three or more episodes) were recruited consecutively and online FENO tests at tidal breathing with multiple breaths were performed. Results. Twenty-seven (84%) out of 32 infants (median age of 12 months) who met the inclusion criteria for this post hoc analysis, successfully performed the FENO determinations. Eighteen (66%) infants were classified with positive stringent API. FENO levels were significantly higher among patients with positive API than those with negative (median [IQR] of 12.3 [14.8] ppb vs. 4.1 [7.9] ppb, respectively, p = .016). Furthermore, FENO and positive API had a significant correlation (Spearman’s rho, ρ = 0.4741, p = .0125). After logistic regression analysis including FENO levels, gender, age, and use of controller therapy, FENO was the only variable that was marginally related to API (OR = 1.12, 95% CI: 0.99–1.27, p = .07). Conclusion. Infants with recurrent wheezing who had a positive stringent API already had higher FENO levels than those with a negative API. This finding needs to be corroborated in a larger prospective study.

Óxido nítrico exhalado e índice predictivo de asma en menores de dos años

Introduction The fraction of exhaled nitric oxide (FE NO) is considered as an indirect marker of eosinophilic inflammation of the airway. In collaborating children the usual method is by a single breath. The impossibility of performing this in non-collaborating children has led to the development of the online and offline tidal breathing technique. The objective of the study has been to analyse the relationship between the multiple breaths online FE NO and the asthma predictive index (API) in children less than 2 years-old. Material and methods An observational and cross-sectional study on a consecutive sample of boys and girls between 2 months and 2 years of age, over a period of 4 months. The post-prandial multiple breaths online FE NO and flow spirometry between 40 and 60 ml/s, using a stationary chemiluminescence analyser (CLD 88 sp). The quantitative variables were: age, weight, IgE, eosinophilia, FE NO, flow spirometry. The qualitative variables were: gender, atopic dermatitis, allergic rhinitis, food and medical allergies, family history of asthma and atopy, diagnosis and treatment. The relationship between API and FE NO was analysed using the exact Fisher and Student t tests and the level of agreement between API and FE NO using Cohen's Kappa. The relationship between eosinophilia, IgE, atopic dermatitis and FE NO was also studied (exact Fisher and Student t tests). Results The cohort consisted of 38 patients. The determinations were successfully carried out on 32 (84.21) of the cases. The mean age was 10.9 ± 5.06 months. The cases with a positive API had significantly higher FE NO values than those with a negative API, with a level of agreement between API and FE NO of 0.71. Conclusions There is a significant relationship and a good level of agreement between the online tidal breathing FE NO and the API.

Fraction of Exhaled Nitric Oxide and Asthma Predictive Index in Infants Less Than Two Years-Old

Introduction The fraction of exhaled nitric oxide (FE NO) is considered an indirect marker of eosinophilic inflammation of the airway. In cooperative children, the usual method is a single breath. The impossibility of performing this in uncooperative children has led to the development of the online and offline tidal breathing technique. The objective of the study has been to analyse the relationship between the multiplebreath online FE NO and the asthma predictive index (API) in children under the age of two. Material and methods An observational and cross-sectional study on a consecutive sample of boys and girls between 2 months and 2 years of age, over a period of 4 months. The post-prandial multiple breaths online FE NO and flow spirometry between 40 and 60 ml/s, using a stationary chemiluminescence analyser (CLD 88 sp). The quantitative variables were: age, weight, IgE, eosinophilia, FE NO, flow spirometry. The qualitative variables were: gender, atopic dermatitis, allergic rhinitis, food and medical allergies, family history of asthma and atopy, diagnosis and treatment. The relationship between API and FE NO was analysed using the exact Fisher and Student t tests and the level of agreement between API and FE NO using Cohen's Kappa. The relationship between eosinophilia, IgE, atopic dermatitis and FE NO was also studied (exact Fisher and Student t tests). Results The cohort consisted of 38 patients. The determinations were successfully carried out on 32 (84.21) of the cases. The mean age was 10.9 ± 5.06 months. The cases with a positive API had significantly higher FE NO values than those with a negative API, with a level of agreement between API and FE NO of 0.71. Conclusions There is a significant relationship and a good level of agreement between the online tidal breathing FE NO and the API.

Do risk factors for persistent asthma modify lung function in infants and young children with recurrent wheeze?

There is very limited information on how the risk of persistent asthma in recurrent wheezing (RW) infants modifies their lung function early in life. The aim of this study is to compare lung function of RW infants and young children with a positive or negative asthma predictive index (API), an index previously used to anticipate asthma persistence into childhood and adolescence. Two groups of RW infants and young children were recruited in two centres in Spain (Palma de Mallorca and Murcia). Lung function was measured according to the thoracho-abdominal compression technique (RCT), and values of the maximal flow at functional residual capacity (V'FRC) were expressed as Z-scores. Other variables included in the study, as independent factors, were: gender, age, length, weight, and parental smoking habits together with information regarding API. Expressed as mean +/- SD, API+ RW infants (n = 50; age in months 11.9 +/- 4.9) had a lower V'FRC Z-score than API- RW ones (n = 41; age in months 12.3 +/- 6.2; -2.01 +/- 0.79 vs. -1.64 +/- 0.77, P = 0.026, respectively). Centre and tobacco exposition did not have an effect on lung function. Among RW infants and young children, those having a positive API have a significant lower lung function as measured by V'FRC at an early age.