Methacholine bronchial provocation test in patients with asthma: serial measurements and clinical significance

BACKGROUND/AIMS: The methacholine bronchial provocation test (MBPT) is used to detect and quantify airway hyper-responsiveness (AHR). Since improvements in the severity of asthma are associated with improvements in AHR, clinical studies of asthma therapies routinely use the change of airway responsiveness as an objective outcome. The aim of this study was to assess the relationship between serial MBPT and clinical profiles in patients with asthma. METHODS: A total of 323 asthma patients were included in this study. The MBPT was performed on all patients beginning at their initial diagnosis until asthma was considered controlled based on the Global Initiative for Asthma guidelines. A responder was defined by a decrease in AHR while all other patients were considered non-responders. RESULTS: A total of 213 patients (66%) were responders, while 110 patients (34%) were non-responders. The responder group had a lower initial PC20 (provocative concentration of methacholine required to decrease the forced expiratory volume in 1 second by 20%) and longer duration compared to the non-responder group. Members of the responder group also had superior qualities of life, compared to members of the non-responder group. Whole blood cell counts were not related to differences in PC20; however, eosinophil concentration was. No differences in sex, age, body mass index, smoking history, serum immunoglobulin E, or frequency of acute exacerbation were observed between responders and non-responders. CONCLUSIONS: The initial PC20, the duration of asthma, eosinophil concentrations, and quality-of-life may be useful variables to identify improvements in AHR in asthma patients.

Role of astograph methacholine provocation test in diagnosis of bronchial asthma / 实用医学杂志

Objective To evaluate the diagnostic value of astograph methacholine provocation test for bronchial asthma.Methods A total of 238 asthma patients and 499 non-asthma patients participated in the detection by astograph methacholine provocation test.Statistical methods were used to analyze the differences of astograph parameters and find the indicators of asthma diagnosis and the critical value.Results Dmin,Cmin and PD15 were much lower in the asthma group (P ＜ 0.01),compared with the the non-asthma group,when SGrs,SGrs/Grs cont were much higher (P ＜ 0.01).SGrs was relevant with Dmin,Cmin,PD15 in the asthma group (P =0.000;r =0.685,r =0.657,r =0.639) as well as the SGrs/Grs cont did (P =0.000,r =0.775;r =0.740,r =0.708).In ROC analysis,Dmin presented an AUC of 0.661,the cutoff value was 2.71 unit,with a sensitivity of 0.739 and specificity of 0.551.PD15 presented an AUC of 0.746,the cutoff value was 4.856 5 unit,with a sensitivity of 0.693 and specificity of 0.684.Conclusion Astograph methacholine provocation test shows good sensitivity and specificity in the diagnosis of asthma,particularly when Dmin ≤ 2.71 Unit or PD15 ≤ 4.8565 Unit as the cutoff value.

Nonspecific Bronchoprovocation Test / 결핵및호흡기질환

Bronchial asthma is a disease characterized by the condition of airway hyper-responsiveness, which serves to produce narrowing of the airway secondary to airway inflammation and/or various spasm-inducing stimulus. Nonspecific bronchoprovocation testing is an important method implemented for the purpose of diagnosing asthma; this test measures the actual degree of airway hyper-responsiveness and utilizes direct and indirect bronchoprovocation testing. Direct bronchoprovocation testing using methacholine or histamine may have superior sensitivity as these substances directly stimulate the airway smooth muscle cells. On the other hand, this method also engenders the specific disadvantage of relatively low specificity. Indirect bronchoprovocation testing using mannitol, exercise, hypertonic saline, adenosine and hyperventilation serves to produce reactions in the airway smooth muscle cells by liberating mediators with stimulation of airway inflammatory cells. Therefore, this method has the advantage of high specificity and also demonstrates relatively low sensitivity. Direct and indirect testing both call for very precise descriptions of very specific measurement conditions. In addition, it has become evident that challenge testing utilizing each of the various bronchoconstrictor stimuli requires distinct and specific protocols. It is therefore important that the clinician understand the mechanism by which the most commonly used bronchoprovocation testing works. It is important that the clinician understand the mechanism of action in the testing, whether direct stimuli (methacholine) or indirect stimuli (mannitol, exercise) is implemented, when the testing is performed and the results interpreted.

Is Performance of a Modified Eucapnic Voluntary Hyperpnea Test in High Ventilation Athletes Reproducible?

PURPOSE: Exercise-induced bronchoconstriction (EIB) is common in “high ventilation” athletes, and the Eucapnic Voluntary Hyperpnea (EVH) airway provocation test is the standard EIB screen. Although the EVH test is widely used, the in-test performance in high ventilation athletes as well as the reproducibility of that performance has not been determined. Reproducibility of pre- and post-test spirometry and self-reported atopy/cough was also examined. METHODS: High ventilation athletes (competitive swimmers; n=11, 5 males) completed an atopy/cough questionnaire and EVH testing (operator controlled FiCO₂) on 2 consecutive days. RESULTS: Swimmers achieved 85%±9% and 87%±9% of target FEV1 volume on days 1 and 2, respectively, (P=0.45; ICC 0.57 [0.00-0.86]) resulting in a total ventilation of 687 vs 684 L [P=0.89, ICC 0.89 (0.65-0.97]) equating to 83%±8% and 84%±9% of predicted total volume (ICC 0.54 [0.00-0.85]) between days 1 and 2. FiCO₂ required to maintain eucapnic conditions was 2.5%. Pre-test FEV1 was less on day 2 (P=0.04; ICC >0.90). Day 1 to 2 post-test FEV1 was not different, and 4 swimmers were EIB positive (>10% fall in pre-post FEV1) on day 1 (3 on day 2). CONCLUSIONS: EVH in-test performance is reproducible however required less FiCO₂ than standard protocol and the swimmers under-ventilated by 125 and 139 L/min for days 1 and 2, respectively. How this affects EIB diagnosis remains to be determined; however, our results indicate a post-test FEV1 fall of ≥20% may be recommended as the most consistent diagnostic criterion.

Clinical features of chronic cough with airway hyper-responsiveness in children / 中华实用儿科临床杂志

Objective To study the clinical features and spirometry of children with chronic cough and positive findings by bronchial provocation test.Methods Four hundred and fifty children with chronic cough from 3 hospitals of Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong Medical University School of Medicine,Gong Li Hospital of Pudong New Area,Pudong Hospital,were enrolled in this study from December 2012 to December 2014,and among them,373 cases completed the questionnaires,spirometry and bronchial provocation test.The differences in clinical features and spirometry between the bronchial provocation test positive group and negative group were compared.And the further evaluation of their clinical value was performed.Results Two hundred and thirty-six cases of children with bronchial provocation tests positive showed much higher rate of dry [72.03％ (170/236 cases)] and night cough[58.90％ (139/236 cases)] than those in the negative group[27.00％ (37/137 cases),22.63％ (31/137cases)],and the differences were significant (x2 =71.154,45.973,all P ＜0.01).Children in positive group also had higher morbidity of eczema[52.12％ (123/236 cases)],allergic conjunctivitis [24.15％ (57/236 cases)] and inhaled allergy history[40.25％ (95/236 cases)] than those in negative group[32.85％ (45/137 cases),10.95％ (15/137cases),18.98％ (26/137 cases)],and there existed significant differences (x2 =13.006,9.701,17.904,all P ＜0.01).And they also had higher asthma heredity [18.22％ (43/236 cases)] than that in negative group [9.49％(13/137 cases)],and the difference was significant (x2 =5.179,P =0.023);with worse small airway function [50.85％ (120/137 cases) vs 36.50％ (50/137 cases)] (x2 =7.197,P =0.007).For further study,the sensitivity and specificity for dry cough were both high(72.03％ and 72.99％).For specificity,family history was the most highest one (90.51％),and night cough and allergic conjunctivitis were also high.Conclusions Pulmonary function tests to reflect small airway function abnormalities,combined with a family history of asthma and chronic cough in children related to eczema,allergic conjunctivitis,and inhalation allergy history clinical features,can better predict airway hyperresponsiveness.

Correlation of gastroesophageal reflux and asthma-like pathophysiological changes / 中华实用儿科临床杂志

Objective To investigate whether gastroesophageal reflux can cause asthma-like pathophysiological changes and its mechanism.Methods Sixty BALB/c mice were randomly divided into 4 groups:group A was gastroesophageal reflux control group,group B was asthma control group,group C was gastroesophageal reflux group,and group D was asthmatic group.The asthmatic models were replicated with ovalbumin(OVA) and aluminum hydroxide,and gastroesophageal reflux models were replicated with hydrochloric acid solution pepsin.After the last inhaling ovalbumin and slow perfusion,the airway pressure was detected,and eosinophil (EOS) and neutrophil granulocyte in bronchial lavage fluid were counted.The flow cytometer was used to determinate IL-4,IFN-γ,and Th1/Th2 ratio changes of spleen cells;Lung tissue and esophagus sections were stained with HE,and pathological changes of lung tissue and esophagus were observed.Results In group C and group D,the airway hyper-responsiveness was significantly increased compared with group A and group B,and the differences were statistically significant (all P ＜ 0.05).In group C and group D,IL-4were significantly increased,while IFN-γand Thl/Th2 ratio were significantly decreased than that in the group A and B group,the differences were statistically significant (all P ＜ 0.05).EOS of group C and group D accounted for a high percentage of total cells and they were significantly higher than that in group A and group B,and the differences were statistically significant (all P ＜ 0.05).Through lung tissue biopsy,in group C and group D,bronchial lumen deformation,infiltration of inflammatory cells around the wall,basement membrane thickening,inflammatory cell infiltration around the wall,peripheral vascular edema,enlarging alveolar cavity,alveolar wall thinning,fracture,part of alveolar fusion into bullace of lung,could be observed.The lung pathological section showed that the endothelial cells in group A and group B were integrated and had no denaturation or necrosis,and there was no inflammation cell infiltrate around.EOS biopsy could be observed in group A and group B of lower esophagus markedly submucosal edema,submucosal inflammatory cell infiltration,and keratin hyper function,visible bacteria group A group B and group D were basic ally normal,with no pathological changes.Conclusions Gastroesophageal reflux can induce Th1/Th2 decreasing,airway hyper-responsiveness and pathophysiological changes similar to asthma.

The predicting value of small airway diseases for asthma in patients with chronic cough / 中国实用内科杂志

Objective The aim of this study is to investigate the correlation between small airway disease and airway hyper-responsiveness,and explore the predicting value of small airway diseases for asthma.Methods Pulmonary function tests and bronchial provocation tests were performed in 249 patients with chronic cough from Sep. 2004 to Sep. 2006.The incidence of small airway disease and airway hyper-responsiveness were observed.Results There were 91 patients with small airway disease,and 103 patients with positive tests for bronchial provocation in total 249 chronic cough patients.The incidence of positive tests for bronchial provocation in 91 patients(73.63%)with small airway disease was significantly higher than that in 158 patients(22.78%)without it,P

On the Kampo Treatment for Bronchial Asthma. Significance of Supplementary Therapy for Jin-hypofunction / 日本東洋医学雑誌

Bronchial asthma is now considered to be caused by airway hyper-responsiveness due to airway inflammation. Accordingly, inhaled corticosteroids, which reduce inflammation, have become the main treatment for this disorder. However, airway hyper-responsiveness would not improve in spite of using inhaled corticosteroids.<br>Kampo medicines such as Sho-seiryu-to, Makyo-Kanseki-to, Eppi-ka-hange-to, Shimpi-to and Saiboku-to are reported to be effective for bronchial asthma. However, it is still difficult to treat adult asthmatic patients by with these Kampo formulae.<br>We reported that Hachimi-jio-gan or Bakumi-jio-gan improved airway hyper-responsiveness and could reduce the doses of corticosteroids, or discontinue corticosteroids in four asthmatic patients. Case 1 is a patient induced by cold weather, Case 2 is a patient with hoarseness, Case 3 is a patient whose attacks are induced with exercise, and Case 4 is an intractable patient with recurrent pulmonary infection. These formulae consist of Rokumi-jio-gan, which is considered a basic prescription for moisturizing the dryness of airway mucosa and improving pulmonary function in Kampo medicine. These results suggest that moisture in airway mucosa following oral administration of these formulae is important to improve airway hyper-responsiveness.