Effects of aeroallergen sensitization on symptom severity, pulmonary function, and bronchodilator response in children with bronchial asthma

Background@#Allergen sensitization, symptom severity, pulmonary function test, and bronchodilator response are important in the diagnosis and treatment of asthma. However, the relationship between these factors remains unclear.@*Objective@#The objective of this study was to investigate the relationship between aeroallergen sensitization and asthma severity, pulmonary function, and bronchodilator response among pediatric patients with bronchial asthma.@*Methods@#This was a prospective study where 155 pediatric patients aged 7–18 years old with bronchial asthma were recruited from Outpatient Clinics. Patients who met the inclusion criteria proceeded with spirometry and aeroallergen skin prick test.@*Results@#There was a significant degree of sensitization, wherein 100% of the patients had sensitization to one or more aeroallergens. Among these children, 106 (68%) were polysensitized. The polysensitized group had more severe and persistent asthma severity profile (p<0.001) and worse pulmonary function (p<0.001). The frequency of abnormal pre-bronchodilator lung function of the polysensitized group was higher than the monosensitized group (p<0.001). A positive bronchodilator response was higher among polysensitized children as compared to monosensitized children (p<0.001). Sensitization to Dermatophagoides farinae, Dermatophagoides pteronyssinus and dog correlated with impairment of both the large airways and distal small airways while sensitization to cat, cockroach, and horse correlated only with impairment of the large airways (p<0.05). Patients sensitized to D. farinae, D. pteronyssinus, cat and dog had significant bronchodilator response (p<0.05).@*Conclusion@#Polysensitized asthmatic children had a more persistent and severe asthma profile, worse pulmonary function, and higher bronchodilator reversibility compared to the monosensitized group.

Usefulness of bronchodilator response as an index of asthma control in children

PURPOSE: Assessing asthma control is important for proper management, and various indices for objective assessment of asthma control, such as fractional exhaled nitric oxide (FeNO) and asthma control test (ACT) score have been proposed. Recently, bronchodilator response (BDR) was reported as a marker of poor asthma control in adults. This study aimed to assess the usefulness of BDR as a biomarker for childhood asthma. METHODS: A total of 305 children diagnosed with asthma were included. Spirometry with bronchodilator test was done at the time of diagnosis and about 14 months after asthma treatment. All children were evaluated by childhood asthma control test (c-ACT) and FeNO after asthma treatment. The patients were divided into 2 groups according to BDR results: the positive and negative BDR groups. Various biomarkers for asthma control, such as c-ACT, FeNO and changes of forced expiratory volume in 1 second (FEV1), were compared between the 2 groups. RESULTS: Of the 305 patients, 143 (46.9%) were positive and 162 (53.1%) were negative for BDR. The BDR-positive group showed lower FEV1. In the BDR positive group, FEV1 was significantly increased after asthma treatment, especially in children with airflow limitation which was defined as below 80% of FEV1 or atopy. In atopic children, BDR showed a significant negative correlation with c-ACT and a positive correlation with FeNO. CONCLUSION: In asthmatic children with airflow limitation at the time of diagnosis, BDR can be a useful index for predicting improvement in lung function by asthma maintenance treatment. BDR could be a reliable marker for the assessment of asthma control in atopic children.

Relationship between Bronchodilator Response, Airway Hyperresponsiveness, and Exhaled Nitric Oxide Levels in Patients with Suspected Bronchial Asthma / 대한내과학회지

BACKGROUND/AIMS: Exhaled nitric oxide (NO) has been extensively investigated as a marker of airway inflammation in asthma, and fractional exhaled nitric oxide (FeNO) is recognized as a useful tool for its evaluation. The aim of this study was to investigate the relationships between FeNO levels and bronchodilator response (BDR), and between FeNO and mannitol-induced airway hyperresponsiveness (AHR), in patients with suspected asthma. METHODS: Clinical variables were collected from patients aged ≥ 13 years with suspected bronchial asthma and measured levels of FeNO. These levels were compared with patient values for forced expiratory volume in the first second (FEV1) and forced expiratory flow at 25 and 75% of the pulmonary volume (FEF(25-75%)) in bronchodilator response tests under control conditions, and during bronchial provocation with mannitol. Correlations and receiver operating characteristic (ROC) curves between FeNO levels and each test were assessed. RESULTS: A total of 259 patients were included in the analysis. The mean ages of the two test groups were 41.1 and 47.8 years, respectively. FeNO levels were strongly correlated with bronchodilator response (%) and with the mannitol dose producing a 15% fall in FEV1 (PD15). On the other hand, FeNO levels were only weakly correlated with FEF(25-75%). The optimal cut-off values for FeNO to predict a positive BDR and AHR were 38.5 and 29.5 parts per billion, respectively. CONCLUSIONS: This study suggests that FEV1 and FEF(25-75%) airway responses correlate with FeNO levels in patients with suspected bronchial asthma. FeNO levels may help to predict positive responses to BDR and AHR.

Respuesta broncodilatadora en niños asmáticos / Bronchodilatador response in asthmatic children

In asthmatic patients the bronchodilator response (BDR) reflects airway obstruction reversibility. BDR commonly used definition of 12 percent or greater change in FEV1 from baseline offers poor sensitivity as an adjunct test in the diagnosis of asthma in children. A cutoff of 8 percent - 10 percent has significantly better sensitivity, although more research studies are needed to recommend this lower BDR value in children. A positive BDR is associated with biomarkers of inflammation, future lung function, inhaled corticosteroids response, and poor asthma control and could provide a useful tool for better monitoring asthmatic children, particularly when pre bronchodilator spirometry is in normal range.

En pacientes asmáticos la respuesta broncodilatadora (RBD) refleja la reversibilidad de la obstrucción de la vía aérea. La definición de 12 por ciento o mayor cambio en VEF1 con respecto a su basal tiene baja sensibilidad y podría llevar a un subdiagnóstico y subtratamiento de asma. La utilización de un punto de corte menor, de 8 por ciento a 10 por ciento, mejora significativamente la sensibilidad para el diagnóstico de asma en niños y podría considerarse en casos individuales, requiriéndose más estudios para recomendar su uso en niños. Una RBD positiva en niños se ha asociado con biomarcadores de inflamación, función pulmonar futura, respuesta a corticoides inhalatorios y pobre control del asma, por lo tanto podría entregar al médico una herramienta más para una mejor evaluación de los niños con asma sobre todo cuando su espirometría basal es normal.

Comparison of Exhaled Nitric Oxide Analyzers in Childhood Asthma / 소아알레르기및호흡기학회지

PURPOSE: The measurement of exhaled nitric oxide (eNO) is a noticeable tool that reflects asthmatic airway inflammation. However, the eNO values might be variable according to the patient's condition and the method of measurement. The aim of this study was to compare the values of eNO measured by two different eNO analyzers in asthmatic children (Niox mino(R) [Aerocrine; Solna, Sweden] and CLD88(R) [Eco Medics; Durten, Switzerland]. METHODS: One hundred four asthmatic children and 59 healthy controls were enrolled. The study participants underwent pulmonary function testing before and after inhaled bronchodilator treatment, a methacholine provocation test, and sputum induction; the eNO concentration was then measured. RESULTS: The value of eNO measured by Niox mino(R) was significantly lower than the value of eNO measured by CLD88(R) (30.7+/-25.0 vs. 38.6+/-29.2 ppb, P <0.001). The intraclass correlation coefficient was 0.786 (P <0.001). The eNO concentration was significantly increased in asthmatic children than controls (38.4+/-27.9 vs. 17.2+/-9.0 ppb, P <0.001 by Niox mino(R); 47.8+/-31.8 vs. 22.2+/-12.7 ppb, P <0.001 by CLD88(R)). The eNO concentration was significantly correlated with the FEV1/FVC (r =-0.382, P <0.001 [Niox mino(R)]; r =-0.273, P =0.001 [CLD88(R)], percent sputum eosinophils (r =0.257, P =0.032 [Niox mino(R)]; r =0.297, P =0.017 [CLD88(R)]), and PC20 (r =-0.333, P <0.001 [by Niox mino(R)] r =-0.240, P =0.003 [CLD88(R)]). CONCLUSION: The measurement of eNO might be a supportive tool for the diagnosis of asthma in children; however, the eNO values differ according to analyzers.

Atopy as a Risk Factor for an Elevated Bronchodilator Response in Children with Asthma / 소아알레르기및호흡기학회지

PURPOSE: The bronchodilator response (BDR) is frequently measured to assess the severity of asthma and to help facilitate therapeutic decisions, as well as to confirm the diagnosis. Few reports are available on the impact of atopy, one of the most important risk factors for childhood asthma, on the BDR. METHODS: The medical records of 207 asthmatic children (174 with atopic asthma and 33 with non-atopic asthma) were retrospectively reviewed. At the time of asthma diagnosis, the subjects underwent blood tests, bronchial provocation tests, and spirometry before and 15 minutes after inhalation of 4 puffs of salbutamol. We compared the mean BDR levels between the children with atopic and non-atopic asthma, then determined the correlations between the BDR and serum markers of eosinophilic inflammation. RESULTS: While the mean pre-bronchodilator FEV1 was not different between children with atopic and non-atopic asthma, atopic asthmatics had a higher mean BDR than non-atopic asthmatics (9.12+/-5.69% vs. 6.93+/-3.80%, P =0.03). There were weak, but significant correlations between the BDR and the serum markers of eosinophilic inflammation (total immunoglobulin E, r =0.192, P =0.01; total eosinophil count, r =0.192, P =0.01; eosinophil cationic protein, r =0.200, P <0.01). CONCLUSION: Asthmatic children had different mean levels of BDR based on atopic status at the time of asthma diagnosis. When the BDR was assessed to aid therapeutic decisions, the presence of atopy should be taken into consideration in children with asthma.

Bronchodilator Response and Its Relationship to Bronchial Hyperresponsiveness in Children with Allergic Rhinitis/Asthma / 소아알레르기및호흡기학회지

PURPOSE: Bronchial impairment has been observed in patients with allergic rhinitis (AR) as well as asthma. Few reports exist on bronchodilator response (BDR) and its relationship with bronchial hyperresponsiveness (BHR) in children with AR. METHODS: A total of 309 children (170 asthmatic children, 80 children with AR and 59 control subjects) were included. After conducting methacholine bronchial provocation and BDR tests, we compared the mean of BDR between the 3 groups and examined the relationships between BDR, prebronchodilator forced expiratory volume in 1 second (FEV(1)) and provocative concentration causing 20% fall in FEV(1) (PC(20)) in both AR and asthmatic patients. RESULTS: Asthmatic children showed a higher mean BDR than those with AR or control subjects. There were significant relationships between BDR, PC(20) and prebronchodilator FEV1 in asthmatic children. Children with AR also showed a higher BDR than control subjects. Though AR children with elevated BDR had lower prebronchodilator FEV1, they showed no significant relationship between BDR and PC(20). CONCLUSION: Children with AR as well as asthma demonstrated an elevated BDR as compared to control subjects. Though the relationship between BDR and BHR in AR subjects was not so remarkable as in asthmatic children, the elevated BDR was associated with the decreased airway caliber in AR patients. These results may reflect the lower airway impairment in children with AR, which suggests a close link between AR and asthma.

The role of inhaled and/or nasal corticosteroids on the bronchodilator response / 소아과

BACKGROUND: To compare the profiles of the bronchodilator response (BDR) among children with asthma and/or allergic rhinitis (AR) and to determine whether BDR in these children is reduced by treatment with inhaled and/or nasal corticosteroid. METHODS: Sixty-eight children with asthma (mean age, 10.9 years), 45 children with comorbid asthma and AR (mean age, 10.5 years), and 44 children with AR alone (mean age, 10.2 years) were investigated. After a 2-week baseline period, all children were treated with inhaled fluticasone propionate (either 100 or 250 microg b.i.d., tailored to asthma severity) or nasal fluticasone propionate (one spray b.i.d. in each nostril) or both, according to the condition. Before and 2 weeks after starting treatment, all children were evaluated with spirometry and bronchodilator testing. BDR was calculated as a percent change from the forced expiratory volume in 1 second (FEV1) at baseline. RESULTS: The mean BDR was 10.3% [95% confidence interval (CI) 8.3-12.4%] in children with asthma, 9.0% (95% CI 7.3-10.9%) in subjects with asthma and AR, and 5.0% (95% CI 4.1-5.9%) in children with AR alone (P<0.001). After treatment, the mean BDR was reduced to 5.2% (95% CI 4.2-6.3%) (P<0.001) in children with asthma and to 4.5% (95% CI 3.5-5.5%) (P<0.001) in children with asthma and AR. However, children with rhinitis showed no significant change in BDR after treatment, with the mean value being 4.7% (95% CI 3.7-5.8%) (P=0.597). CONCLUSION: The findings of this study imply that an elevated BDR in children with AR cannot be attributed to nasal inflammation alone and highlights the close relationship between the upper and lower airways.

Immediate Effect of Hemodialysis on Pulmonary Function and Bronchodilator Response in Patients with Chronic Renal Failure / 결핵

BACKGROUND: We hypothesized that there was a relationship between body weight change and bronchodilator response (BDR) in patients with chronic renal failure (CRF) on hemodialysis (HD). Several mechanisms such as pulmonary edema due to water retention or increased permeability of alveolar capillary may play a important role in pulmonary function impairment and bronchial hyperresponsiveness in patients with CRF on HD. But, no studies have been published concerning BDR in patients with CRF on HD. This study was aimed to know the immediate effect of hemodialysis on pulmonary function and BDR in patients with CRF on HD. METHODS: This study included 30 patients with CRF on HD. We collected data including age, sex, height, pretibial and pedal pitting edema, interdialysis weight gain, postdialysis weight loss , underlying diseases, duration of HD, FEV1, FVC, FEV1/FVC, and BDR before and after HD. RESULTS: Interdialysis weight gain of the patients was 3.4 +/- 1.0 kg, and postdialysis weight loss was 3.2 +/- 0.7 kg. Before HD, FEV1, FVC, and FEV1/FVC of the patients were 89 +/- 22%, 86 +/- 19% of predicted, and 87 +/- 10 %. After bronchodilator inhalation, these parameters were changed to 95 +/- 22%, 90 +/- 19% of predicted, and 88 +/- 9% respectively. BDR was positive in 15 patients. After HD, FEV1, FVC, and FEV1/FVC of the patients were 100 +/- 23%, 94 +/- 18% of predicted, and 88 +/- 11%. After bronchodilator inhalation, these parameters were changed to 102 +/- 23%, 96 +/- 18% of predicted, and 89 +/- 8% respectively. BDR was positive in 9 patients. CONCLUSION: First, HD increases FEV1, FVC, and FEV1/FVC but little affects BDR. Second, there is no correlation between postdialysis weight loss and increases in FEV1, FVC, and FEV1/FVC after HD. Third, there is also no correlation not only between interdialysis weight gain and BDR before HD but between postdialysis weight loss and BDR after HD.

The Relation Between Bronchodilator Response, Airway Hyperresponsiveness and Serum Eosinophil Cationic Protein (ECP) Level in Moderate to Severe Asthmatics / 결핵

BACKGROUND: Bronchial asthma is characterized by a reversible airway obstruction, airway hyperresponsiveness, and eosinophilic airway inflammation. The bronchodilator response(BDR) after short acting beta agonist inhalation and PC20 with methacholine inhalation are frequently used for diagnosing bronchial asthma, However, the relationship between the presence of a bronchodilator response and the degree of airway hyperresponsiveness is uncertain. Therefore, the availability of a eosinophil cationic protein(ECP) and a correlation ECP with a bronchodilator response and airway hyperresposiveness was investigated. METHOD: A total 71 patients with a moderate to severe degree of bronchial asthma were enrolled and divided into two groups. 31 patients with a positive bronchodilator response and 38 patients with a negative bronchodilator response were evaluated. In both groups, the serum ECP, peripheral blood eosinophil counts, and total IgE level were measured and the methacholine bronchial provocation test was examined. RESULTS: There were no differences observed in age, sex, atopy, and baseline spirometry in both groups. The peripheral eosinophil counts showed no difference in both groups, but the ECP level in group 1 (bronchodilator responder group) was higher than in group 2(non-bronchodilator responder group) (22.4±20.7 vs 14.2±10.4, mean±SD). The PC20 in group 1 was significantly lower than in group 2 (1.14±1.68 vs 66±2.98). There was a significant positive correlation between the BDR and ECP, and a negative correlation between the bronchial hyperresponsiveness and ECP. CONCLUSION: The bronchodilator response significantly correlated with the bronchial hyperresponsiveness and serum ECP in the moderate to severe asthma patients. Hence, the positive bronchodilator response is probably related with active bronchial inflammation and may be used as a valuable index in treatment, course and prognosis of bronchial asthma.