Hyperresponsiveness In Children Research Articles

The role of respiratory infections in the formation of airway hyperresponsiveness in children

Airway hyperresponsiveness (AHR) is a heterogeneous and complex disorder characterized by excessive narrowing of the airways in response to various exogenous and endogenous stimuli. This article presents information from the last five years, including 50 publications from PubMed and Google Scholar, on the most common viruses that provoke the development of airway hyperresponsiveness in children, including respiratory syncytial virus, rhinovirus, metapneumovirus, influenza and parainfluenza viruses, SARS-CoV-2 coronavirus, adenovirus, and bocavirus. It describes a number of pathophysiological mechanisms by which viruses damage the respiratory epithelium and lead to the formation of infectious and post-infectious bronchial hypersensitivity. The role of hyperexpression of cytokines and inflammatory mediators in the development of AHR, especially in early childhood, is emphasized. It is shown that the inflammatory process and a balanced immune response are crucial for mitigating the severity of the disease caused by viruses. Understanding the molecular mechanisms of inflammatory reactions and the immune response to acute respiratory viral infections can help develop more effective methods for the prevention and treatment of respiratory diseases in children.

Comment on the article “Use of methacoline challenge test to detect bronchial hyperresponsiveness”

Dear Editor;
 We read with interest the article titled “Use of methacoline challenge test to detect bronchial hyperresponsiveness in children with persistent rhinitis” published in Cukurova Medical Journal by Guc et al. [1]. 
 This study showed that BHR positivity is high in children with allergic rhinitis. Allergic rhinitis can cause false positive BHR. In addition, smoking and COPD can cause false positives [2, 3]. COPD can occur in childhood [4]. We think that it would be appropriate to mention this in the discussion part of this study.

Use of methacoline challenge test to detect bronchial hyperresponsiveness in children with persistent rhinitis

Purpose: The incidence of persistent rhinitis in childhood is increasing day by day. Since bronchial hyperreactivity (BHR) and asthma can also be seen in a significant proportion of patients with persistent rhinitis, the use of markers that may indicate the risk of developing asthma in these patients is very important in clinical follow-up. In this study, it was aimed to demonstrate the relationship between persistent rhinitis and asthma in childhood using the bronchial methacoline challenge test (BMCT) and to investigate other factors associated with the risk of developing asthma in patients with persistent rhinitis.
 Materials and Methods: Patients aged 6-18 years who presented with findings of persistent rhinitis were evaluated with a detailed history, physical examination, and spirometry. Patients with normal examination findings and spirometry findings, and patients whose examination findings and nasal inflammation findings were compatible with moderate-to-severe rhinitis were included in the study, and their atopy status was evaluated by skin prick test, and their BHR was evaluated by BMCT.
 Results: Seventy-three patients were included in the study. The mean age was 9±2.7years, 45.2% of the patients were male. 63% of the patients were allergic and family history of allergy was present in 45.2% of the patients. 82.2% of the patients had BHR detected with BMCT. The median blood eosinophil count (BEC) was 320/mm3 and the IgE level was 160kU/L. Patients with atopy had statistically significantly higher IgE and BEC values compared with non-allergic patients. Patients with BHR were found to be younger, and had higher median BEC values. In multivariant analysis, it was observed that the patient's age300/mm3, and IgE levels>250IU/L increased the probability of detecting BHR with BMCT. 
 Conclusion: Care should be taken for every patient with persistent rhinitis because of the risk of BHR and asthma. Atopy examinations should be performed, but the possibility of developing BHR and asthma should not be overlooked even in the patients who are non- allergic.

Cytokine Hyperresponsiveness in Children With ETV6::RUNX1-positive Acute Lymphoblastic Leukemia After Challenge With Common Pathogens.

Cytokine Hyperresponsiveness in Children With ETV6::RUNX1-positive Acute Lymphoblastic Leukemia After Challenge With Common Pathogens.

Allergic sensitisation did not affect bronchial hyper-responsiveness in children without respiratory tract symptoms.

The potential for immunotherapy to prevent asthma development has become a hot topic. This prompted us to revisit data from an early study that examined allergic sensitisation on bronchial hyperresponsiveness (BHR) in children with and without respiratory symptoms. Unlike previous studies, it used both indirect and direct test methods. The study was conducted in Kuopio, Finland, in 1994 and 247 children (55.1% boys) with a mean age 10.5±1.7years were recruited using a school survey: 165 with lower respiratory symptoms and 82 healthy controls. Each child underwent a 6-min free-running test and a methacholine test with a cumulative dose of 4900µg. All participants underwent skin-prick tests: 127were sensitised and 120 were non-sensitised. There were no significant differences in lung function between the sensitised and non-sensitised children. However, sensitisation was associated with BHR which was measured by both the methacholine test (2400µg versus >4900µg, p<0.001) and the free-running test (-3.5% versus -2.6%, p=0.042). No such differences were observed among the healthy controls. Sensitisation was a predictor of allergic diseases, and only multisensitisation to a minimum of four allergens increased the incidence of asthma. Allergic sensitisation did not affect BHR in children without respiratory symptoms.

Leukotriene D4 bronchial provocation test for detection of airway hyper-responsiveness in children

To explore the value of leukotriene D4 (LTD4) bronchial provocation test (BPT) in detection of airway hyper-responsiveness (AHR) in children. A total of 151 children aged 6 to 14 years, including 86 in remission of asthma and 65 with acute bronchitis, who were followed up in our respiratory clinic between November, 2017 and August, 2018. The children were randomly divided into LTD4 group (78 cases) and methacholine (MCH) group (73 cases). In LTD4 group, the 78 children underwent LTD4-BPT, including 46 with asthma and 32 children having re-examination for previous episodes of acute bronchitis; in MCH group, the 73 children underwent MCH-BPT, including 40 with asthma and 33 with acute bronchitis. MCH-BPT was also performed in the asthmatic children in the LTD4 group who had negative responses to LTD4 after an elution period. The major adverse reactions of the children to the two BPT were recorded. The diagnostic values of the two BPT were evaluated using receiver-operating characteristic (ROC) curve. There was no significant difference in the results of basic lung function tests between LTD4 group and MCH group (P&gt;0.05). The positive rate of BPT in asthmatic children in the LTD4 group was significantly lower than that in the MCH group (26.1% vs 72.5%; P &lt; 0.05). The positive rate of BPT in children with previous acute bronchitis in the LTD4 group was lower than that in the MCH group (3.1% vs 15.2%). The positive rate of MCH-BPT in asthmatic children had negative BPT results in LTD4 group was 58.8%, and their asthma was mostly mild. The sensitivity was lower in LTD4 group than in MCH group (0.2609 vs 0.725), but the specificity was slightly higher in LTD4 group (0.9688 vs 0.8485).The area under ROC curvein LTD4 group was lower than that in MCH group (0.635 vs 0.787). In children with asthma in the LTD4 group, the main adverse reactions in BPT included cough (34.8%), shortness of breath (19.6%), chest tightness (15.2%), and wheezing (10.9%). The incidence of these adverse reactions was significantly lower in LTD4 group than in MCH group (P &lt; 0.05). Serious adverse reactions occurred in neither of the two groups. LTD4-BPT had high safety in clinical application of children and was similar to the specificity of MCH-BPT. However, it had low sensitivity, low diagnostic value, and limited application value in children's AHR detection.

TNF-α (rs1800629) polymorphism modifies the effect of sensitization to house dust mite on asthma and bronchial hyperresponsiveness in children

Asthma is a complex disease, with various genetic and environmental factors implicated in its development. Sensitization to the house dust mite (HDM) is closely linked with the development of respiratory allergies, including asthma. However, some children sensitized to HDM do not complain of any symptoms of respiratory allergies, even though HDM is correlated with an increased risk for developing asthma, suggesting the involvement of other factors. Tumor necrosis factor (TNF)-α is associated with the pathophysiologies of asthma in combination with its genetic polymorphism. The aim of the present study was to elucidate the associations between sensitization to HDM, polymorphism of TNF-α rs1800629, and asthma/bronchial hyperresponsiveness (BHR). Our results revealed that sensitization to HDM is associated with asthma diagnosis in lifetime, current asthma, and BHR in Korean children. Furthermore, the genetic polymorphism of TNF-a rs1800629 was found to modify and interact with these associations. This study suggests that prevention strategies for childhood asthma need to be targeted according to genetic susceptibility.

House dust mite sensitization is associated with bronchial hyperresponsiveness in children with allergic rhinitis

House dust mite sensitization is associated with bronchial hyperresponsiveness in children with allergic rhinitis

Impulse Oscillometry Discerns the Peripheral Airway Response to an Inhaled Bronchodilator between Obese and Nonobese Children

IntroductionImpulse oscillometry (iOS) is a useful tool to distinguish between central and peripheral airway resistance. For example, iOS has shown that peripheral airway resistance is greater in children with versus those without obesity, despite no difference in FEV1. Considering the added peripheral airway resistance in children with obesity, we sought to determine if iOS can detect potential differences in the peripheral airway response to an inhaled bronchodilator (BD) between children with and those without obesity.MethodsTwenty‐four children with and eleven without obesity, ages 8–12yrs, completed iOS and spirometry testing before and 15mins after the administration of four puffs of an inhaled BD (Ventolin®, 90μg). A mixed models ANOVA (group by pre‐to‐post‐BD) was used to determine differences in FEV1, plethysmographic airway resistance (Raw) and specific Raw (sRaw), and iOS parameters associated with airway resistance. These parameters include resistance at 5 Hz, 10 Hz (R5 and R10: total airway resistance), 20 Hz (R20: large airway resistance), and the difference between R5 and R20 (R5–20: peripheral airway resistance). Reactance at 5 Hz (X5: total airway elastic recoil) and the area under the reactance‐frequency curve (AX: index of small airway patency) were also measured using iOS.ResultsThere was no difference in FEV1 (% pred) or FEV1/FVC between groups and none of our participants showed a positive BD response based on the conventional method of a ≥12% increase in FEV1. Compared with children without obesity, children with obesity presented a greater baseline R5 (7.28 ± 1.20 vs. 5.42 ± 1.44 cmH2O·L−1·s−1; p=0.001), R10 (6.04 ± 1.12 vs. 4.58 ± 1.07 cmH2O·L−1·s−1; p=0.002), R20 (4.76 ± 0.95 vs. 3.94 ± 0.79 cmH2O·L−1·s−1; p=0.025), R5–20 (2.52 ± 0.64 vs. 1.49 ± 0.75 cmH2O·L−1·s−1; p&lt;0.001), and AX (7.65 ± 5.59 vs. 3.75 ± 1.97 cmH2O·L−1; p=0.008), with no difference in X5 (−1.19 ± 0.77 vs. −1.19 ± 0.33 cmH2O·L−1; p=0.667). A group by pre‐to‐post‐BD interaction was found for R5 (p=0.033) and R10 (p=0.024). Both R5 and R10 decreased to a greater extent with BD in children with obesity versus children without obesity (R5: −20.8 ± 9.5% vs. −12.8 ± 15.2%; R10: −21.6 ± 8.6% vs. −14.5 ± 13.1%). In all children (n=35), Raw, sRaw, and all iOS parameters, except for X5, decreased with the BD (p&lt;0.05).ConclusionIn addition to greater central and peripheral airway resistance in children with obesity, iOS also detected a greater peripheral airway response to a BD in children with obesity. Although no established criteria exist for children ages 8–12yrs, the American Thoracic Society defines an airway response in preschool children as a 20–40% decrease in R5 and a 15–30% decrease in R10. Based on these criteria, our finding that R5 and R10 dropped by 20.8% and 21.6% in children with obesity indicates potential peripheral airway hyperresponsiveness in children with obesity. However, further research is warranted to establish the meaning of, or normal criteria for, peripheral airway responsiveness in prepubescent children.Support or Funding InformationNIH R01 HL136643, Texas Health Presbyterian Hospital Dallas, King Charitable Foundation Trust, and Dr. Pepper Snapple.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Peak expiratory flow rate assessment to screen for asthma in children with allergic rhinitis

Background: Allergic rhinitis is a common disease affecting around 10-25% of the population worldwide. There is a temporal relationship between the onset of allergic rhinitis and asthma and the ‘unified airway hypothesis’ explains this. Many researchers have demonstrated bronchial hyper-responsiveness prior to onset of asthma symptoms further validating this hypothesis. Further many studies favour treating allergic rhinitis may prevent the onset of asthma. So, detecting allergic rhinitis earlier and treating it adequately is of vital importance. The aims and objectives of this study is to identify bronchial hyper responsiveness in children with allergic rhinitis, prior to the onset of asthmatic symptoms, by measuring PEFR and its clinical correlates.Methods: A prospective observational study was conducted in Department of Paediatrics in Sree Balaji Medical College and Hospital. Inclusion and Exclusion Criteria were defined, and the study was conducted on a total of 85 children. After taking informed consent from parents, the children coming under the study population were analyzed for their baseline characteristics and PEFR is measured using a low reading Mini Wright peak flow meter and compared with mean value of south Indian children using the formula, PEFR= {(HEIGHT IN CM-100) X5} +100.Results: The mean PEFR as expressed in percentage of expected PEFR is 77.28% in males and 83.34% in females. The mean percentage of expressed PEFR does not vary significantly between different age groups. Of the 85 children,48(56.5%) have mild intermittent allergic rhinitis,28(32.9%) have mild persistent allergic rhinitis,5(5.9%) have moderate-severe intermittent allergic rhinitis and 4(4.7%) have moderate-severe persistent allergic rhinitis. There were 37(43.5%) blockers (with predominant nose block) and 48(56.5%) runners (with predominant rhinorrhea).Conclusions: PEFR is abnormal in 41.2% of children with allergic rhinitis. PEFR reduces linearly as the severity of allergic rhinitis increases. PEFR decreases as the number of cardinal symptoms increases. PEFR increases significantly after treatment of allergic rhinitis alone.

Association Between Sensitization to Mold and Impaired Pulmonary Function in Children With Asthma.

PurposeRecent data indicate that sensitization to mold contributes to the severity and persistence of asthma. In this study, we investigated the relationships between sensitization to mold and lung function parameters in children with asthma.MethodsWe retrospectively reviewed clinical data from 551 asthmatic subjects. We selected subjects who met clinical diagnostic criteria of asthma. Their spirometry, methacholine challenge tests, and measurements of blood eosinophils, serum IgE, eosinophil cationic protein (ECP) and fractional exhaled nitric oxide (FeNO) results were included. Skin prick testing (SPT) results with 13 common aeroallergens in Korea including house dust mites, animal dander, pollen, cockroach and mold were reviewed. Subjects were divided into 3 groups according to their SPT results. Subjects who showed no positive result to any aeroallergen were designated as group 1 (non-sensitized). Group 2 represented subjects who were sensitized to aeroallergens other than mold (other allergen-sensitized) and group 3 included subjects who were sensitized to mold allergens (mold-sensitized).ResultsAmong the 551 asthmatic subjects, 67 (12.2%) were sensitized to mold and 366 (66.4%) were sensitized to other aeroallergens. The log mean IgE levels were higher in groups 2 (5.96±1.14 IU/mL) and 3 (5.81±0.97 IU/mL) compared to group 1 (3.88±1.68 IU/mL). Blood eosinophils, ECP and FeNO concentrations were significantly higher in groups 2 and 3, but no significant difference was found between the 2 groups. The mean FEV1 value was significantly lower in group 3 (86.9±12.1%pred) than in groups 2 (92.0±14.8%pred) and 1 (93.4±15.4%pred). The log mean methacholine PC20 was significantly lower in group 3 (0.08±1.91 mg/mL) than in groups 2 (1.31±1.69 mg/mL) and 1 (2.29±1.66 mg/mL).ConclusionsWe observed a differential association between mold and other aeroallergen sensitization, and severity of asthma. Sensitization to mold is associated with lower lung function and increased airway hyper-responsiveness in children with asthma. Mold sensitization could be an important factor determining asthma severity particularly airflow limitation in children.

Механизмы формирования высокой кашлевой готовности у детей с рецидивирующим бронхитом

The process of recurrent bronchitis is accompanied by increased threshold sensitivity of the bronchi to inflammatory mediators, the occurrence of which affect brain activity with a predominance of irritation meso diencephalic structures, autonomic tone, manifesting hypersympathicotonia and increase the level of central regulation contour, cerebral hemodynamics, characterized by increased tone of arterioles and veins , peripheral vascular resistance and venous outflow obstruction. The emerging of bronchial hyperresponsiveness in children with recurrent bronchitis leads to bronchial obstruction at all levels of the bronchial tree, furthermore it leads to reduction of redundant lung capacity and is, apparently, one of the pathogenic mechanisms of persistent flow of inflammatory changes in the bronchi and increased cough readiness.

Somatosensory Event-Related Potentials and Association with Tactile Behavioral Responsiveness Patterns in Children with ASD

The goal of this study was to explore neural response to touch in children with and without autism spectrum disorder (ASD). Patterns of reduced (hypo-responsiveness) and enhanced (hyper-responsiveness) behavioral reaction to sensory input are prevalent in ASD, but their neural mechanisms are poorly understood. We measured event-related potentials (ERP) to a puff of air on the fingertip and collected parent report of tactile hypo- and hyper-responsiveness in children with ASD (n = 21, mean (SD) age 11.25 (3.09), 2 female), and an age-matched typically developing comparison group (n = 28, mean (SD) age 10.1 (3.08, 2 female). A global measure of ERP response strength approximately 220-270 ms post-stimulus was associated with tactile hypo-responsiveness in ASD, while tactile hyper-responsiveness was associated with earlier neural response (approximately 120-220 ms post-stimulus) in both groups. These neural responses also related to autism severity. These results suggest that, in ASD, tactile hypo- and hyper-responsiveness may reflect different waypoints in the neural processing stream of sensory input. The timing of the relationship for hyper-responsiveness is consistent with somatosensory association cortical response, while that for hypo-responsiveness is more consistent with later processes that may involve allocation of attention or emotional valence to the stimulus.

Assessing direct and indirect airway hyperresponsiveness in children using impulse oscillometry

BackgroundAirway hyperresponsiveness (AHR) is a hallmark of asthma but its assessment is usually restricted to older children who are capable of performing the maneuvers involved in spirometry. In younger children, a feasible option to perform the lung function measurement is impulse oscillometry (IOS), which requires less cooperation. ObjectiveTo evaluate whether assessment of AHR by IOS could differentiate children with various obstructive symptoms from one another. MethodsOne hundred twenty-one children (median age 6.0 years, range 3.7–8.1 years) were examined: 31 with probable asthma characterized by current troublesome lung symptoms, 61 with a history of early wheezing disorder (recurrent wheezing ≤24 months of age), 15 with a history of bronchopulmonary dysplasia, and 14 healthy controls. Indirect AHR was assessed by exercise and mannitol challenge tests, and direct AHR was assessed with methacholine using IOS. AHR to exercise was defined as an increase of at least 40% in respiratory resistance at 5 Hz. In the mannitol and methacholine challenges, the dose causing an increase of 40% in respiratory resistance at 5 Hz was calculated. ResultsAHR to exercise was good at differentiating children with current troublesome lung symptoms from those in the other groups (P < .001). AHR to methacholine separated children with current troublesome lung symptoms, early wheezing disorder, and bronchopulmonary dysplasia from the controls (P < .001), whereas the mannitol test did not distinguish among the study groups (P = .209). ConclusionThe methacholine and exercise challenge tests with IOS identify children with probable asthma characterized by troublesome lung symptoms and therefore may represent a practical aid in the evaluation of AHR in young children.

Extended Nitric Oxide Analysis and Bronchial Hyperresponsiveness In Children With Asthma According To Atopy

Extended Nitric Oxide Analysis and Bronchial Hyperresponsiveness In Children With Asthma According To Atopy

Asthma and Airway Hyperresponsiveness in Children with Eosinophilic Esophagitis: EGF and FGF-2 As a Link

Asthma and Airway Hyperresponsiveness in Children with Eosinophilic Esophagitis: EGF and FGF-2 As a Link

小児の肺機能検査・気道過敏性検査

小児の肺機能検査・気道過敏性検査

Autism and peripheral hearing loss: A systematic review

ObjectiveTo systematically review the literature describing the relationship between autism spectrum disorder (ASD) and peripheral hearing loss including literature recommendations for audiological assessment and auditory habilitation in cases where peripheral hearing loss and ASD coexist. Data sourcesPublished studies indexed in MEDLINE (1948–2011). Review methodsThe search strategy identified 595 potential studies. After a review of the titles, 115 abstracts were reviewed and 39 articles were retrieved and assessed independently by at least two authors for possible inclusion. 22 articles pertained to children with ASD and peripheral hearing loss, hearing assessment in children with ASD, audiological habilitation for children with ASD or hyper-responsiveness in children with ASD. 17 further studies were garnered from the reference section of the 22 papers. ResultsControversy exists in the literature regarding prevalence of hearing impairment among individuals with ASD. In cases where ASD and hearing impairment co-exist, diagnosis of one condition often leads to a delay in diagnosing the other. Audiological assessment can be difficult in children with ASD and test–retest reliability of behavioural thresholds can be poor. In cases where hearing impairment exists and hearing aids or cochlear implantation are recommended, devices are often fit with special considerations for the child with ASD. Hyper-responsiveness to auditory stimuli may be displayed by individuals with ASD. Evidence or the suspicion of hyper-responsiveness may be taken into consideration when fitting amplification and planning behavioural intervention. ConclusionsPrevalence rates of hearing impairment among individuals with ASD continue to be debated. At present there is no conclusive evidence that children with ASD are at increased risk of peripheral hearing loss. A complete audiological assessment is recommended in all cases where ASD is suspected so as not to delay the diagnosis of hearing impairment in the event that hearing loss and ASD co-exist. Objective assessment measures should be used to confirm behavioural testing in order to ensure reliability of audiological test results. Fitting of hearing aids or cochlear implantation are not contraindicated when hearing loss is present in children with ASD; however, success with these devices can be variable.

Predictive Risk Factors for Airway Hyperresponsiveness in Children with Exercise-Induced Respiratory Symptoms

Predictive Risk Factors for Airway Hyperresponsiveness in Children with Exercise-Induced Respiratory Symptoms

Forced expiratory flow between 25% and 75% of vital capacity as a predictor for bronchial hyperresponsiveness in children with allergic rhinitis

Purpose: Allergic rhinitis (AR) is regarded as a risk factor for asthma and bronchial hyperresponsiveness (BHR) is frequently observed in patients with AR. The purpose of this study is to analyze the characteristics of AR patients with BHR and identify factors that contribute to the incidence of BHR. Methods: The medical records of a total of 176 children with AR were analyzed retrospectively. All patients were evaluated by performing spirometry and a methacholine challenge test. Results: One hundred and fifty-five patients (88%) were classified as the BHR-negative group and 21 patients (12%) were classified as the BHR-positive group. Forced expiratory flow between 25% and 75% of vital capacity (FEF25-75 %predicted) was reduced, and total eosinphil counts, total immunoglobulin E (IgE) level, and serum specific IgE levels of Dermatophagoides pteronyssinus and Dermatophagoides farinae were higher in the BHR-positive group compared to the BHR-negative group. However, FEF25-75 was the only statistically significant predictor for the presence of BHR on multivariate logistic regression analysis. The cutoff value to distinguish BHR-positive subjects obtained from a receiver operating characteristics curve of FEF25-75 was 88.4%. A higher frequency of BHR was found in the group with a FEF25-75 less than 88.4%, and the sensitivity, specificity, positive predictive value and negative predictive value were 57.1%, 80.6%, 28.6%, and 93.3%, respectively. Conclusion: Reduced FEF25-75 values in children with AR can be helpful in predicting BHR. Children with low FEF25-75 in spirometric tests should be followed closely for apparent onset of clinical symptoms of asthma. (Allergy Asthma Respir Dis 1?1):60-66, 2013)Allergy Asthma Respir Dis 1(1):60-66, 2013)