Comparison between exhaled nitric oxide and bronchial challenge with methacholine or adenosine-5'-monophosphate in the diagnosis of childhood asthma

PURPOSE: Asthma is a chronic airway inflammatory disease characterized by bronchial hyperresponsiveness and reversible airway obstruction. Bronchial challenge with methacholine or adenosine-5'-monophosphate (AMP) has been used to diagnose asthma. Recently, measurement of exhaled nitric oxide (eNO) can also be used for the diagnosis of asthma. The aim of this study was to compare the diagnostic value for asthma between challenge with methacholine or AMP and eNO in children with chronic nonspecific respiratory symptoms. METHODS: One hundred thirty-three children who have chronic nonspecific respiratory symptoms were enrolled. Bronchial challenge with methacholin and AMP were performed, and eNO was measured in all subjects. Subjects were defined as asthma based on the clinical symptoms and bronchodilator response during follow-up of at least 3 months after test. RESULTS: Thirty-three subjects (34%) were finally diagnosed as asthma among 97 patients after 3-month follow-up. The area under the receiver operating characteristic curves for the diagnosis of asthma were 0.903 (95% confidence interval [CI], 0.838-0.969; P<0.001) for methacholline challenge, 0.867 (95% CI, 0.783-0.950; P<0.001) for AMP challenge, and 0.588 (95% CI, 0.467-0.709, P=0.156) for eNO measurement. The cutoff values of these tests were methacholine PC20 (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second) 12.0 mg/mL (sensitivity, 87.9%; specificity, 82.8%), AMP PC20 566.2 mg/mL (sensitivity, 84.8%; specificity, 85.9%), and eNO 18.5 ppb (sensitivity, 45.5%; specificity, 71.9%). CONCLUSION: Measurement of eNO may be inferior to challenge with methacholine and AMP for the diagnosis of asthma in children.

The Relationship between Wheezing during Methacholine Bronchial Challenge and the Severity of Acute Asthma Exacerbation in Asthmatic Children / 소아알레르기및호흡기학회지

PURPOSE:Global Initiatives for Asthma (GINA guideline) 2005 suggests that the pitch and intensity of wheezing as the determinating factor for the severity of asthma exacerbation. However, there have not yet been sufficient data to support the correlation between wheezing and the severity of asthma exacerbation. This study was aimed to estimate the relationship between wheezing threshold and the level of forced expiratory volume in 1 second (FEV1). METHODS:Among 370 pediatric patients who visited Inha University Hospital between May 2005 and June 2006, who underwent the methacholine bronchial challenge tests in order to diagnose asthma, 228 patients with PC20 less than 16 mg/mL were examined. Medical history, physical examination, skin prick test, eosinophil count and total IgE level in peripheral blood, and nasal smear for eosinophil count were performed. RESULTS:Among the 228 patients 127 (55.7%) showed wheezing during the methacholine challenge test. Among the patient with wheezing 82 patients (36%) showed more than 20% fall of FEV1, and the other, 45 patients (19.7%), showed less than 20% FEV1%fall. One hundred one patients (43.3 %) did not show any wheezing until the %fall of FEV1 was below 20%. The geometric mean (range of 1SD) [2.29 (0.86-6.13) mg/mL] of methacholine PC20 of the 127 patients with wheezing was significantly lower than that [4.11 (1.82-9.24) mg/mL] of the 101 patients without wheezing (P<0.001). The geometric mean (range of 1SD) of methacholine PC20 in the 143 patients with positive skin prick test results was 2.57 (0.97-6.81) mg/mL, which was significantly lower than that of the 37 patients with negative results [3.69 (1.57-8.66) mg/mL] (P<0.001). CONCLUSION:We could learn that most wheezing patients showed more than 20% fall of FEV1. Therefore, it is suggested that the asthmatic children with wheezing were regarded and treated as moderate or more severe state

Asthma Progression and Airway Inflammation Assessed by Lung Function in Children with Asthma / 소아알레르기및호흡기학회지

PURPOSE: The social and economic impact of asthma is remarkable worldwide. To date, there have been many unanswered questions about factors related to asthma progression and persistence. This study focused on possible risk factors for persistent asthma that had developed between infancy and late childhood. METHODS: Sixty-seven children with persistent mild-to-moderate asthma were enrolled in this study. They were classified into 2 groups according to the Global Initiative for Asthma (GINA) guideline 2006: early-onset (3 years, n=39) asthmatics. All patients were interviewed on the personal and familial history of atopy, breast feeding, parental smoking and the recent use of inhaled corticosteroids. We performed spirometry, and skin prick tests and measured body mass index, serum allergen-specific IgE, serum eosinophil counts and serum ECP in asthmatics. All asthmatics underwent the bronchial challenge by methacholine inhalation and outdoor free running. RESULTS: Risk factors such as eczema and frequent wheezing were more common in early-onset asthmatics than in late-onset asthmatics (P0.05). Inhaled corticosteroids were more frequently used in early-onset asthmatics than in late-onset asthmatics (P<0.0001). A reciprocal relationship between FEV1/FVC and the duration of asthma was also detected in persistent asthmatics (n=57, r=-0.398, P=0.002). CONCLUSION: The results of this study suggest that atopic dermatitis and frequent wheezing may be important risk factors for the persistence of asthma and lung function decline from early to late childhood.

The Diagnostic Value of the Fractional Exhaled Nitric Oxide for Asthma / 中国呼吸与危重监护杂志

Objective To determine the diagnostic value of fractional exhaled nitric (FeNO) measurement in diagnosis of bronchial asthma. Methods The patients with unkown-cause respiratory symptoms including wheezing, cough, and breathlessness were enrolled from August to September in 2008. FeNO was measured by nitric oxide analyzer (NIOX; Aerocrine AB; Solna, Sweden). Bronchial challenge test (BCT) or bronchodilator test was defined as golden standard for asthma diagnosis. The value of FeNO was assessed and the optimal operating point of FeNO testing was determined by the means of the receiver operating characteristic (ROC) curves. Results A total of 101 patients were enrolled, in which 48 cases were diagnosed as asthma by positive yield in BCT (in 38 cases) or bronchodilator test (in 10 cases). The severity of airway hyperresponsiveness (AHR) judged by BCT was mild in 15 cases, moderate in 15 cases and severe in 8 cases. The levels of FeNO of asthma group were higher than those of non-asthma group [(68.19±43.00) pph vs (19.52±10.60) ppb, P < 0.05]. A linear correlation of FeNO with lnPD20 FEV1 was revealed in the cases with AHR. Area under ROC curve was 0.9. The optimal diagnostic cutoff point was 36.5 ppb which was capable of differentiating asthma and non-asthma with sensitivity of 92.7%, specificity of 83.3%, positive predictive value of 79.17% , negative predictive value of 94.34% and accuracy of 87.13%. Conclusion FeNO test may be helpful in the diagnosis of asthma with high sensitivity and specificity.

Protective effect of bronchial challenge with hypertonic saline on nocturnal asthma

Inhalation of hypertonic saline (HS) causes bronchoconstriction in asthmatic subjects. Repeated inhalation of HS leads to substantially reduced bronchoconstriction, known as the refractory period. Refractoriness due to different stimuli has also been described (cross-refractoriness). Nocturnal asthma is defined as an increase in symptoms, need for medication, airway responsiveness, and/or worsening of lung function that usually occurs from 4 to 6 am. Our objective was to determine the effect of refractoriness on nocturnal asthma. The challenge test consisted of inhalations of 4.5 percent saline with increasing durations until a reduction of 20 percent in forced expiratory volume in 1 s (FEV1) (PD20HS) or total time of 15.5 min. Twelve subjects with nocturnal asthma were challenged with HS at 16:00 and 18:00 h and FEV1 was measured at 4:00 h. One to 2 weeks later, FEV1 was determined at 16:00 and 4:00 h. LogPD20HS at 18:00 h was significantly greater than logPD20HS at 16:00 h, 0.51 ± 0.50 and 0.69 ± 0.60 mg, respectively (P = 0.0033). When subjects underwent two HS challenges in the afternoon, mean (± SD) FEV1 reduction was 206 ± 414 mL or 9.81 ± 17.42 percent. On the control day (without challenge in the afternoon) FEV1 reduction was 523 ± 308 mL or 22.75 ± 15.40 percent (P = 0.021). Baseline FEV1 values did not differ significantly between the control and study days, 2.48 ± 0.62 and 2.36 ± 0.46 L, respectively. The refractory period following HS challenges reduces the nocturnal worsening of asthma. This new concept may provide beneficial applications to asthmatic patients.

Clinical Significance of Methacholine Bronchial Challenge Test in Differentiating Asthma From COPD / 결핵및호흡기질환

BACKGROUND: Although airway hyper-responsiveness is one of the characteristics of asthma. bronchial hyper-responsiveness has also been observed to some degree in patients with chronic obstructive pulmonary disease (COPD). Moreover, several reports have demonstrated that a number of patients have both COPD and asthma. The methacholine bronchial challenge test (MCT) is a widely used method for the detecting and quantifying the airway hyper-responsiveness, and is one of the diagnostic tools in asthma. However, the significance of MCT in differentiating asthma or COPD combined with asthma from pure COPD has not been defined. The aim of this study was to determine the role of MCT in differentiating asthma from pure COPD. METHOD: This study was performed prospectively and was composed of one hundred eleven patients who had undergone MCT at Chonbuk National University Hospital. Sixty-five asthma patients and 23 COPD patients were enrolled and their MCT data were analyzed and compared with the results of a control group. RESULT: The positive rates of MCT were 65%, 30%, and 9% in the asthma, COPD, and control groups, respectively. The mean PC20 values of the asthma, COPD, and control groups were 8.1+/-1.16 mg/mL, 16.9+/-2.21 mg/mL, and 22.0+/-1.47 mg/mL, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of MCT for diagnosing asthma were 65%, 84%, 81%, and 69%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of MCT (ed note: please check this as I believe that these values correspond to the one PC20 value. Please check my changes.) at the new cut-off points of PC20 < or = 16 mg/ml, were 80%, 75%, 78%, and 78%, respectively. CONCLUSION: MCT using the new cut-off point can be used as a more precise and useful diagnostic tool for distinguishing asthma from pure COPD.

A case of bronchial asthma due to Tyrophagus putrescentiae in a non occupational setting / 천식및알레르기

Storage mites are believed one of the most important allergens in farmers and rural regions. Tyrophagus putrescentiae, belonging to storage mites, is found not only within storehouses but also in the house dust, and the third most common mites following Dermatophagoides farinae and Dermatophagoides pteronyssinus in house dust in Korea. The sensitization rate to Tyrophagus putrescentiae was reported as high as that of house dust mite in patients visiting the allergy clinic in large cities in Korea. We experienced a 69-year-old man who had suffered from dyspnea, wheezing, and coughing for 10 years. He retired from the teaching profession, and had lived in a large city, Deajeon. The skin prick test showed a positive reaction to Tyrophagus putrescentiae and negative reactions to house dust mites. The bronchial challenge test with Tyrophagus putrescentiae showed late asthmatic reaction. We confirmed a Tyrophagus putrescentiae-induced asthma in non occupational setting.

Asthma prevalence among high school students in East Jakarta, 2001, based on ISAAC questionnaire.

The aim of this study was to assess asthma prevalence in children between 13-14 years of age in East Jakarta. This study is a cross sectional study which surveyed 2234 high school students between the ages of 13 and 14 years in East Jakarta in 2001 using the ISAAC questionnaire. Bronchial challenge test was applied by using methacholine substance to 186 students. Reports based on the ISAAC questionnaire indicate that 7.2% of teenage have had wheezing experience, 4.1% have wheezing within the last 12 months, 1.8% have ever suffered severe asthma attack within the last 12 months, 3.3% have suffered wheezing after exercise, and 6.3% have got night cough while they were not suffering from cold. Prevalence of atopy diseases such as rhinitis and eczema were 14.2% and 3.9%, meanwhile rhinitis and eczema prevalence within the last 12 months according to this study were 10.6% and 2.9% respectively. Statistically, there is a significant correlation between wheezing symptom and atopy (p < 0.05). From indepth questionnaire, a significant value of kappa 0.84 related with wheezing within the last 12 months was found. Bronchial challenge test results indicate that sensitivity was 90%, specificity 83.58%, positive predictive value 68.12% and negative predictive value was 95.73%. Asthma prevalence in East Jakarta at 2001 based on ISAAC questionnaire was 8.9%, and cumulative prevalence 11.5%. The ISAAC questionnaire can be used to study asthma prevalence in children at multicenter in Indonesia.