The role of bronchial challenge test in guiding therapy in preschool children with atypical recurrent respiratory symptoms.

OBJECTIVE: This retrospective observational cohort study aimed to assess the real-life application of bronchial challenge test (BCT) in the management of preschool children presenting with atypical recurrent respiratory symptoms (ARRS). METHODS: We included children aged 0.5-6 years referred to a pediatric-pulmonology clinic who underwent BCT using methacholine or adenosine between 2012 and 2018 due to ARRS. BCT was considered positive based on spirometry results and/or wheezing, desaturation, and tachypnea reactions. We collected data on demographics, BCT results, pre-BCT and post-BCT treatment changes, and 3-6 months post-BCT compliance and symptom control. The primary outcome measure was the change in treatment post-BCT (step-up or step-down). RESULTS: A total of 228 children (55% males) with a mean age of 4.2 ± 0.6 years underwent BCT (52% adenosine-BCT, 48% methacholine-BCT). Children referred for methacholine were significantly younger compared with adenosine (3.6 ± 1.2 vs. 4.2 ± 1.2 years, p < .01). Methacholine and adenosine BCTs were positive in 95% and 61%, respectively. Overall, changes in management were observed in 122 (53.5%) children following BCT, with 83 (36.4%) being stepped up and 37 (17%) being stepped down. Significantly more children in the methacholine group were stepped up compared with the adenosine group (46% vs. 28%, p = .004). During the follow-up assessment, we observed a clinical improvement in 119/162 (73.4%) of the children, with nearly 87% being compliant. CONCLUSION: This study demonstrates the importance of BCT in the management of preschool children presenting to pediatric pulmonary units with ARRS. The change in treatment and subsequent clinical improvement observed highlight the added value of BCT to the pulmonologist.

The link between early childhood lower airway symptoms, airway hyperresponsiveness, and school-age lung function.

BACKGROUND: The role of early airway hyperresponsiveness (AHR) in the lung function of school-age children is currently unclear. OBJECTIVE: To conduct a prospective follow-up study of lung function in schoolchildren with a history of lower airway symptoms and AHR to methacholine in early childhood and to compare the findings to schoolchildren with no previous or current lung diseases. We also explored symptoms and markers of type 2 inflammation. METHODS: In 2004 to 2011, data on atopic markers, lung function, and AHR to methacholine were obtained from 193 symptomatic children under 3 years old. In 2016 to 2018, a follow-up sample of 84 children (median age, 11 years; IQR, 11-12) underwent measurements of atopic parameters, lung function, and AHR to methacholine. Moreover, in 2017 to 2018, 40 controls (median age, 11 years; IQR, 9-12) participated in the study. RESULTS: Schoolchildren with early childhood lower airway symptoms and increased AHR had more frequent blood eosinophilia than their peers without increased AHR and lower prebronchodilator forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity Z-scores than those without increased AHR and controls. Post-bronchodilator values were not significantly different between the two AHR groups. Atopy in early childhood (defined as atopic eczema and at least 1 positive skin prick test result) was associated with subsequent lung function and atopic markers, but not AHR. CONCLUSION: In symptomatic young children, increased AHR was associated with subsequent obstructive lung function, which appeared reversible by bronchodilation, and blood eosinophilia, indicative of type 2 inflammation.

Based on what parameters is safe to discontinuate inhaled corticosteroids in children with asthma?

OBJECTIVE: Remission of childhood asthma has not been widely studied. Patients in clinical remission continue to have some degree of bronchial hyperresponsiveness (BHR). The aim of this study was to investigate whether clinical parameters and lung function test are good parameters for discontinuation of inhaled corticosteroids (ICS) in asthmatic children, including patients with persistent BHR, as measured by the methacholine challenge test (MCT). METHODS: One year after discontinuation of inhaled corticosteroids (ICS), MCT was performed in a group of 40 asthmatic children to confirm or exclude BHR. In all patients, ICS treatment was discontinued based on the same parameters: symptoms, spirometry, daily PEF, and negative bronchodilator test. After achieving complete asthma control for at least 6 to 12 months, ICS treatment was stepped down and discontinued. Clinical course and spirometry were followed up after ICS discontinuation. RESULTS: Positive MCT was found in 50% of the patients. There was no statistically significant difference between the positive and negative MCT groups in age at initiation and discontinuation of ICS therapy, duration of ICS therapy, duration of stepping down period, FEV1, and PEF at the time of withdrawal of ICS and one year later. ICS treatment had to be restarted in two patients from the positive MCT group, due to recurrence of asthma symptoms. CONCLUSION: Clinical parameters, normal spirometry, daily PEF values, and a negative bronchodilator test are good parameters for discontinuing ICS treatment in asthmatic children, even in patients with persistent BHR. Children should continue to be monitored, as symptoms may recur.

Differences in lung function, bronchial hyperresponsiveness and respiratory health between elite athletes competing in different sports.

The aim of this study was to examine lung function, bronchial hyperresponsiveness (BHR) and exercise-induced respiratory symptoms in elite athletes performing different sports. Norwegian national-team athletes (30 swimmers, 32 cross-country skiers, 16 speed-skaters, 11 rowers/paddlers, 17 handball players and 23 soccer players) completed a validated questionnaire, measured exhaled nitric oxide (FENO), spirometry, methacholine provocation (PD20met) and skin prick test. Three cut-off levels defined BHR; i.e. PD20met ≤2 µmol, ≤4 µmol and ≤8 µmol. Mean forced vital capacity (FVC) was highest in swimmers (Mean z-score[95%CI] = 1.16 [0.80, 1.51]), and close to or higher than reference values according to the Global Lung Initiative equation, across all sports. Mean forced expiratory volume in 1 s (FEV1) was higher than reference values in swimmers (0.48 [0.13, 0.84]), and ball game athletes (0.69 [0.41, 0.97]). Mean forced expiratory flow between 25 and 75% of FVC (FEF25-75), and/or FEV1/FVC were lower than reference values in all endurance groups. BHR defined by ≤2 and ≤8 µmol methacholine was observed in respectively 50%-87% of swimmers, 25%-47% of cross-country skiers, 20%-53% of speed-skaters, 18%-36% of rowers/paddlers, and 0%-17% of the ball game athletes. Exercise-induced symptoms were common in all groups, most frequent in cross-country skiers (88%), swimmers (83%) and speed-skaters (81%).HighlightsSwimmers and ball game athletes had higher mean FVC and FEV1 when compared to the reference values predicted by the Global Lung Initiative (GLI) reference equation. Contrasting this, across all sports except ball game athletes, mean FEF25-75 and/or FEV1/FVC were lower than reference values.The prevalence of bronchial hyperresponsiveness (BHR) was high among elite athletes competing in swimming, cross-country skiing, speed skating and rowing/paddling, with swimmers being most affected.The majority of the elite athletes reported exercise-induced respiratory symptoms independent of lung function or BHR.

Allergic sensitization pattern as a marker of bronchial hyperresponsiveness in allergic rhinitis patients living in temperate continental climate zone.

BACKGROUND: Bronchial hyperresponsiveness (BHR) is a key feature of asthma, but it may also appear in allergic rhinitis. The type of allergen, as well as regional characteristics, play an important role in the development of BHR. The aim of our study was to analyze allergen sensitization patterns and the factors that affect BHR in allergic rhinitis patients living in temperate continental climate zone. METHODS: This study retrospectively analyzed allergic rhinitis patients from Eastern Slovakia who underwent skin-prick tests to aeroallergens, spirometry, histamine and methacholine bronchial provocation tests for evaluation of lower airway symptoms. We analyzed the associations between BHR and the pattern of aeroallergen sensitization, lung function parameters, and the total IgE and eosinophil levels. RESULTS: Out of 365 allergic rhinitis patients (age range 16-64 years), 114 showed BHR. Sensitization to house dust mites (HDMs) and grass were the most common. BHR was significantly associated with sensitization to dogs (odds ratio, OR = 2.15, 95% confidence interval, CI: 1.13-4.11) and Alternaria (OR = 2.15, 95% CI: 1.06-4.35); however, BHR did not show a relationship with HDMs sensitization. The levels of total IgE and eosinophils were higher in the BHR-positive group. Sensitization to more than six allergens significantly increased the probability of BHR (p < 0.01). CONCLUSION: Dogs and Alternaria, but not HDMs, were the sensitizing agents most closely associated with BHR. High-grade sensitization and increased total IgE and eosinophil levels were characteristic clinical signs in BHR-positive allergic rhinitis patients in the temperate continental climatic zone.

Predictors of Airway Hyperresponsiveness in Symptomatic Children with Normal Spirometry and Suspicious of Possible Asthma.

BACKGROUND: Asthma diagnosis may be challenging particularly in patients with mild symptoms without an obstructive pattern in spirometry. Detection of airway hyperresponsiveness (AHR) by a positive methacholine challenge (MCC) is still an important diagnostic tool to confirm the presence of asthma with reasonable certainty. However, it is time consuming and could be exhausting for patients. We aimed to identify the predictive factors for AHR in children with respiratory symptoms without obstructive pattern in spirometry. METHODS: Data from children who had undergone MCC were analyzed retrospectively. The demographic features of patients along with laboratory results were collected. RESULTS: A total of 123 children with a median age of 10.5 years were enrolled. AHR was detected in 81 children (65.8%). The age of the children with AHR was significantly younger. The prevalences of aeroallergen sensitization, nocturnal cough, wheezing, and a baseline forced expiratory flow at 75% of vital capacity (FEF75) <65% were significantly more frequent in children with AHR. Multivariate logistic regression analysis revealed age, ever wheezing, nocturnal cough, tree pollen allergy, and FEF75 <65% as independent predictors of AHR. A weighted clinical risk score was developed (range, 0-75 points). At a cutoff point of 35, the presence of AHR is predicted with a specificity of 90.5% and a positive predictive value of 91.5%. CONCLUSION: In children suspected of having asthma, but without an obstructive pattern in the spirometry, combining independent predictors, which can be easily obtained in clinical practice, might be used to identify children with AHR.

Assessment and outcomes of firefighter applicants with possible asthma.

BACKGROUND: Firefighter applicants (FFAs) with a history of asthma may be refused entry to the fire service because of potentially putting themselves and others at risk. AIMS: We undertook a service evaluation to identify respiratory and employment outcomes of FFAs with a history of asthma who had undergone additional respiratory assessment at our specialist occupational lung disease clinic during 2005-19. METHODS: We reviewed FFA medical records and categorized them as having either no current asthma or definite/probable asthma at the time of clinic assessment. 'No current asthma' was defined as negative non-specific bronchial hyper-responsiveness (BHR) to histamine/methacholine, and no symptoms or treatment within the 2 years before clinic. 'Definite/probable current asthma' was defined as either positive BHR, or negative BHR with symptoms and/or treatment within the previous 2 years. Around 1 year later, we contacted FFAs to enquire about their application outcome and current respiratory symptoms. RESULTS: Data were available on 116 applicants; of whom, 45% (n = 52) had definite/probable current asthma and were significantly more likely to be older, atopic to common aeroallergens, report atopic disease and have a lower forced expiratory volume in one second/forced vital capacity ratio compared with applicants with no current asthma. Only two individuals' applications were rejected due to asthma. At follow-up, just 2 (2%) of the 90 operational firefighters reported any recent trouble with asthma. CONCLUSIONS: A history of asthma alone is not sufficient to determine current asthma in FFAs. Even with a diagnosis of current asthma, FFAs are mostly successful in their application to join the fire service.

A pilot study of differential gene expressions in patients with cough variant asthma and classic bronchial asthma.

BACKGROUND: Despite extensive exploration of asthma, the mechanism of asthma has not been fully elucidated. Cough variant asthma (CVA) is considered as precursor to classical asthma (CA). Comparative study between CA and CVA may be helpful in further understanding the pathogenesis of asthma. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from CVA, CA and healthy adults. Each group consisted of five cases. Total RNA was extracted from the PBMCs. Agilent 4 × 44 K human genome oligo microarray was used to detect whole genome expression. Allogeneic clustering, Gene Ontology and KEGG analysis were performed to investigate differentially expressed genes (DEGs). Then, ten candidate genes were screened and verified by real-time PCR. RESULTS: Gene expressions were significantly different among the three groups, with 202 DEGs between the CA and the CVA groups. The Gene Ontology analysis suggested that the DEGs were significantly enriched in 'histone H4-K20 demethylation' and 'antigen processing and presentation of endogenous antigens'. HDC, EGR1, DEFA4, LTF, G0S2, IL4, TFF3, CTSG, FCER1A and CAMP were selected as candidate genes. However, the results of real-time PCR showed that the expression levels of FCER1A, IL4 and HDC in the cough variant asthma group were significantly different from those in the other two groups (p < 0.05). CONCLUSIONS: The pathogenesis of CVA and CA may be related to genes such as FCER1A, HDC and IL4. Further studies incorporating a larger sample size should be conducted to find more candidate genes and mechanisms.

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

AIM: 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. METHODS: The study was conducted in Kuopio, Finland, in 1994 and 247 children (55.1% boys) with a mean age 10.5 ± 1.7 years 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 4900 µg. All participants underwent skin-prick tests: 127were sensitised and 120 were non-sensitised. RESULTS: 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 (2400 µg versus >4900 µg, 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. CONCLUSION: Allergic sensitisation did not affect BHR in children without respiratory symptoms.

Does bronchial hyperresponsiveness predict a diagnosis of cough variant asthma in adults with chronic cough: a cohort study.

Bronchial hyperresponsiveness is a typical, but non-specific feature of cough variant asthma (CVA). This study aimed to determine whether bronchial hyperresponsiveness may be considered as a predictor of CVA in non-smoking adults with chronic cough (CC). The study included 55 patients with CC and bronchial hyperresponsiveness confirmed in the methacholine provocation test, in whom an anti-asthmatic, gradually intensified treatment was introduced. The diagnosis of CVA was established if the improvement in cough severity and cough-related quality of life in LCQ were noted.The study showed a high positive predictive value of bronchial hyperresponsiveness in this population. Cough severity and cough related quality of life were not related to the severity of bronchial hyperresponsiveness in CVA patients. A poor treatment outcome was related to a low baseline capsaicin threshold and the occurrence of gastroesophageal reflux-related symptoms. In conclusion, bronchial hyperresponsiveness could be considered as a predictor of cough variant asthma in non-smoking adults with CC.

Can bronchial challenge test with adenosine or methacholine at preschool age predict school-age asthma?

OBJECTIVE: Bronchial challenge test (BCT) measures current airways-hyperreactivity, however, its predictive role in pre-school children (<6 years) for the diagnosis of asthma at school age is still debatable. We aimed to find whether preschool children with a positive adenosine or methacholine BCT are more prone to asthma at school age. METHODS: We included children aged 6-13 years with respiratory symptoms that were previously referred to our pulmonary function laboratory for BCT (methacholine or adenosine, depending on the question asked) at age 10 months to 6 years (baseline). BCT was considered positive based on spirometry results or wheezing, desaturation, and tachypnea reactions. The primary outcome measure was asthma diagnosis at school age using the well-validated International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. We used logistic regression analysis to explore whether positive BCT could predict school-age asthma while including age and collected modified asthma predictive index in the model. RESULTS: One hundred and fifty-one of 189 children (53% males), completed the ISAAC questionnaire (response rate = 80%). Mean ages at BCT and at follow-up were 3.9 ± 1.28 and 9.4 ± 1.85 years, respectively. At baseline, 40 of 67 had a positive adenosine test and 73 of 84 had a positive methacholine BCT. Thirty-nine children were diagnosed with asthma at school age. Logistic regression analysis showed that a positive adenosine test at pre-school age was the best predictor, significantly increasing the odds of asthma at school age by 6.34 (95% CI: 1.23-32.81, p = .028), while methacholine did not show significance (p = .69). CONCLUSION: Choosing the relevant BCT for the question asked, positive adenosine, but not methacholine test, at pre-school, may predict asthma at school age.

Bronchial hyperresponsiveness is common in Hanoi, Vietnam: Asthma probably underdiagnosed.

BACKGROUND: Bronchial hyperresponsiveness (BHR) is a key pathophysiological feature of asthma. Methacholine challenge test (MCT) is a common bronchoprovocation test useful for confirming a diagnosis of asthma. Studies of BHR in the general population of Asian countries are rare. AIM: To estimate prevalence and determinants of BHR in Hanoi, Vietnam, and to study the association between BHR and symptoms common in asthma and previously diagnosed asthma. METHODS: 1500 out of 5872 randomly selected adults in urban and rural Hanoi, who had participated in a questionnaire survey (83% participated), were randomly selected and invited to clinical examinations. Totally 684 subjects (46%) participated. MCT was performed in 366 subjects. BHR was defined as a FEV1-decrease of ≥20% from baseline following methacholine inhalations (PC20). Cut offs used in the analyses were PC20 ≤ 1 mg/ml, ≤2 mg/ml and ≤8 mg/ml. RESULTS: The prevalence of BHR was 16.4% at doses ≤8 mg/ml, while 9.6% reacted on doses ≤2 mg/ml. PC20 ≤ 2 mg/ml was associated with FEV1 <80% of predicted. PC20 ≤ 2 mg/ml, but not PC20 ≤ 8 mg/ml, was associated with multi-sensitization to airborne allergens. BHR defined as PC20 ≤ 8 mg/ml was associated with age >45y. The combination of asthmatic wheeze (wheezing with breathlessness apart from colds) and BHR, irrespectively of magnitude of BHR, was more common than the combination of BHR with previously diagnosed asthma. CONCLUSIONS: The results indicate BHR to be more common in Hanoi than previously found in south-east Asia. Although the prevalence of physician diagnosed asthma has increased in Vietnam, our results indicate that asthma still may be underdiagnosed in Vietnam.

Current Asthma Prevalence Using Methacholine Challenge Test in Korean Children from 2010 to 2014.

BACKGROUND: Most epidemiological studies depend on the subjects' response to asthma symptom questionnaires. Questionnaire-based study for childhood asthma prevalence may overestimate the true prevalence. The aim of this study was to investigate the prevalence of "Current asthma" using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and methacholine challenge test in Korean children. METHODS: Our survey on allergic disease included 4,791 children (age 7-12 years) from 2010 to 2014 in Korean elementary schools. Bronchial hyperresponsiveness (BHR) was defined as provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20) ≤ 16 mg/mL. "Current asthma symptoms" was defined as positive response to "Wheezing, current," "Treatment, current," or "Exercise, current." "Current asthma" was defined when the subjects with "Current asthma symptoms" showed BHR on the methacholine challenge test or had less than 70% of predicted FEV1 value. RESULTS: The prevalence of "Wheezing, ever," "Wheezing, current," "Diagnosis, ever," "Treatment, current," "Exercise, current," and "Current asthma symptoms" was 19.6%, 6.9%, 10.0%, 3.3%, 3.5%, and 9.6%, respectively, in our cross-sectional study of Korean elementary school students. The prevalence of BHR in elementary school students was 14.5%. The prevalence of BHR in children with "Wheezing, ever," "Wheezing, current," "Diagnosis, ever," "Treatment, current," and "Exercise, current" was 22.3%, 30.5%, 22.4%, 28.8%, and 29.9%, respectively. BHR was 26.1% in those with "Current asthma symptoms." The prevalence of "Current asthma" was 2.7%. CONCLUSIONS: Our large-scale study provides 2.7% prevalence of current asthma in Korean elementary school children. Since approximately one third of the children who have "Current asthma symptoms" present BHR, both subjective and objective methods are required to accurately predict asthma in subjects with asthma symptoms.

Baseline spirometry parameters as predictors of airway hyperreactivity in adults with suspected asthma.

BACKGROUND: Methacholine challenge tests (MCTs) are used to diagnose airway hyperresponsiveness (AHR) in patients with suspected asthma where previous diagnostic testing has been inconclusive. The test is time consuming and usually requires referral to specialized centers. Simple methods to predict AHR could help determine which patients should be referred to MCTs, thus avoiding unnecessary testing. Here we investigated the potential use of baseline spirometry variables as surrogate markers for AHR in adults with suspected asthma. METHODS: Baseline spirometry and MCTs performed between 2013 and 2019 in a large tertiary center were retrospectively evaluated. Receiver-operating characteristic curves for the maximal expiratory flow-volume curve indices (angle ß, FEV1, FVC, FEV1/FVC, FEF50%, FEF25-75%) were constructed to assess their overall accuracy in predicting AHR and optimal cutoff values were identified. RESULTS: A total of 2983 tests were analyzed in adults aged 18-40 years. In total, 14% of all MCTs were positive (PC20 ≤ 16 mg/ml). All baseline spirometry parameters were significantly lower in the positive group (p < 0.001). FEF50% showed the best overall accuracy (AUC = 0.688) and proved to be useful as a negative predictor when applying FEF50% ≥ 110% as a cutoff level. CONCLUSIONS: This study highlights the role of FEF50% in predicting AHR in patients with suspected asthma. A value of ≥ 110% for baseline FEF50% could be used to exclude AHR and would lead to a substantial decrease in MCT referrals.

Identifying bronchoconstriction from the ratio of diaphragm EMG to tidal volume.

BACKGROUND: A fall of ≥ 20 % in forced expiratory volume in the first second (FEV1) with a cumulative dose of histamine ≤ 7.8 µmol is considered to indicate bronchial hyperactivity, but no method exists for patients who cannot perform spirometry properly. Here we hypothesized that increases in respiratory central output measured by chest wall electromyography of the diaphragm (EMGdi-c) expressed as a function of tidal volume (EMGdi-c/VT) would have discriminative power to detect a 'positive' challenge test. METHODS: In a physiological study EMGdi was recorded from esophageal electrode (EMGdi-e) in 16 asthma patients and 16 healthy subjects during a histamine challenge test. In a second study, EMGdi from chest wall surface electrodes (EMGdi-c) was measured during a histamine challenge in 44 asthma patients and 51 healthy subjects. VT was recorded from a digital flowmeter during both studies. RESULTS: With histamine challenge test the change in EMGdi-e/VT in patients with asthma was significantly higher than that in healthy subjects (104.2 % ± 48.6 % vs 0.03 % ± 17.1 %, p < 0.001). Similarly there was a significant difference in the change of EMGdi-c/VT between patients with asthma and healthy subjects (90.5 % ± 75.5 % vs 2.4 % ± 21.7 %, p < 0.001). At the optimal cut-off point (29 % increase in EMGdi-c/VT), the area under the ROC curve (AUC) for detection of a positive test was 0.91 (p < 0.001) with sensitivity 86 % and specificity 92 %. CONCLUSIONS: We conclude that EMGdi-c/VT may be used as an alternative for the assessment of bronchial hypersensitivity and airway reversibility to differentiate patients with asthma from healthy subjects.

Increased risk of asthma at age 10 years for children sensitized to multiple allergens.

BACKGROUND: Childhood sensitization patterns have been previously found to be related to variable risk of early life allergic disease in several birth cohorts. OBJECTIVE: To determine whether these risks persist into later childhood. METHODS: In the birth cohort of the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study, previous latent class analysis based on sensitization to 10 allergens found the following 4 early life sensitization patterns at age 2 years: "highly sensitized," "milk/egg dominated," "peanut and inhalant(s)," and "low to no sensitization." At an age 10 study-specific visit, children were evaluated by an allergist for current asthma and atopic dermatitis through a physical examination and interviews with the child and parent or guardian. Total and specific immunoglobulin E (IgE), spirometry, and methacholine challenge were also completed. RESULTS: Compared with children sensitized to none or 1 allergen, children sensitized to 4 or more food and inhalant allergens at age 2 had the highest risk of current asthma (relative risk [RR], 4.42; 95% confidence interval [CI], 2.58-7.59; P < .001) and bronchial hyperresponsiveness (RR, 1.77; 95% CI, 1.29-2.42; P < .001). In addition, they had the highest levels of total IgE (geometric mean, 800 IU/mL; 95% CI, 416-1536) among the 4 groups. Risk of current atopic dermatitis did not depend on pattern of sensitization but remained increased for children with any sensitization (RR, 2.23; 95% CI, 1.40-3.55; P < .001). No differences in spirometry (forced expiratory volume in 1 second, forced expiratory flow between 25% and 75%, and forced expiratory volume in 1 second/forced vital capacity) were identified. CONCLUSION: The previously reported importance of a specific pattern of sensitization in early life (sensitization to ≥4 inhalant and food allergens) continues to be associated with an increased risk of asthma, bronchial hyperresponsiveness, and high total IgE at age 10 years.

Lung function trajectories and bronchial hyperresponsiveness during childhood following severe RSV bronchiolitis in infancy.

BACKGROUND: Children with severe respiratory syncytial virus (RSV) bronchiolitis in infancy have increased risks of asthma and reduced lung function in later life. There are limited studies on the longitudinal changes of lung function and bronchial hyperreactivity from early to late childhood in infants hospitalized for RSV bronchiolitis. METHODS: In a prospective cohort of 206 children with their first episode of RSV-confirmed bronchiolitis in the first year of life, 122 had spirometry performed at least twice between 5-16 years of age. Methacholine bronchoprovocation was available in 127 and 79 children at 7 and 12 years of age, respectively. Longitudinal changes in FEV1 , FVC, and FEV1 /FVC z-scores and methacholine PC20 were analyzed. RESULTS: 55% of the study cohort (N = 122) were male, and 55% were Caucasian. During follow-up, longitudinal changes in z-scores for pre- and post-bronchodilator FEV1 (P < .0001) FVC (P < .0001) and FEV1 /FVC (P < .0001 for pre- and 0.007 for post-bronchodilator) from age 5 to 10-16 years were observed. Declined lung function in late childhood was significantly associated with gender, physician diagnosis of asthma, and allergic sensitization. PC20 geometric mean increased from 0.28 mg/mL at 7 years to 0.53 mg/mL at 12 years of age, and the frequency of abnormal bronchial hyperreactivity decreased from 96% to 78% (P = .0003). CONCLUSIONS: Following severe RSV bronchiolitis, there appear to be significant longitudinal changes in pre- and post-bronchodilator lung function during childhood. The study has several limitations including significant dropouts and the lack of a control group and post-bronchodilator measurements. Bronchial hyperreactivity is common in children following severe RSV bronchiolitis; however, it appears to decrease as they enter late childhood.

Lysophosphatidic Acid Regulates the Differentiation of Th2 Cells and Its Antagonist Suppresses Allergic Airway Inflammation.

BACKGROUND: Lysophosphatidic acid (LPA), a prototypic member of a large family of lysophospholipids, has been recently shown to play a role in immune responses to respiratory diseases. The involvement of LPA in allergic airway inflammation has been reported, but the mechanism remains unclear. OBJECT: We analyzed the biological activity of LPA in vitro and in vivo and investigated its role in allergic inflammation in mice using an LPA receptor 2 (LPA2) antagonist. METHODS: We used a murine model with acute allergic inflammation, in which mice are sensitized and challenged with house dust mite, and analyzed airway hyperresponsiveness (AHR), pathological findings, Th2 cytokines, and IL-33 in bronchoalveolar lavage fluid (BALF) and lung homogenates. The effect of LPA on Th2 differentiation and cytokine production was examined in vitro using naive CD4+ T cells isolated from splenocytes. We also investigated in vivo the effects of LPA on intranasal administration in mice. RESULTS: The LPA2 antagonist suppressed the increase of AHR, the number of total cells, and eosinophils in BALF and lung tissue. It also decreased the production of IL-13 in BALF and IL-33 and CCL2 in the lung. LPA promoted Th2 cell differentiation and IL-13 production by Th2 cells in vitro. Nasal administration of LPA significantly increased the number of total cells and IL-13 in BALF via regulating the production of IL-33 and CCL-2-derived infiltrating macrophages. CONCLUSION: These findings suggest that LPA plays an important role in allergic airway inflammation and that the blockade of LPA2 might have therapeutic potential for bronchial asthma.