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Background: Adenosine monophosphate (AMP) may reflect airway inflammation and hyperresponsiveness, but relationship between AMP and histamine (His, a conventional stimulus) bronchial provocation test (BPT) in asthma is not fully elucidated., Objectives: To compare both BPTs and determine their utility in reflecting changes of asthmatic symptoms., Methods: BPTs were performed in a cross-over fashion, at 2-4 day intervals. Cumulative doses eliciting 20% FEV 1 fall (PD 20 FEV 1 ), diagnostic performance and adverse events (AEs) were compared. Patients with PD 20 FEV 1 lower than geometric mean were defined as responders, otherwise poor responders. Patients with uncontrolled and partly controlled asthma, who maintained their original inhaled corticosteroids therapy, underwent reassessment of airway responsiveness and asthmatic symptoms 3 and 6 months after., Results: Nineteen uncontrolled, 22 partly controlled and 19 controlled asthmatic patients and 24 healthy subjects were recruited. Lower PD 20 FEV 1 geometric means were associated with poorer asthma control in His-BPT (0.424 μmol vs 1.684 μmol vs 3.757 μmol), but not AMP-BPT (11.810 μmol vs 7.781 μmol vs 10.220 μmol). Both BPTs yielded similar overall diagnostic performance in asthma (area under curve: 0.842 in AMP-BPT vs 0.850 in His-BPT). AEs, including wheezing and tachypnea, were similar and mild. Ten patients with uncontrolled and 10 partly controlled asthma were followed-up. At months 3 and 6, we documented an increase in PD 20 FEV 1 -AMP and PD 20 FEV 1 -His, which did not correlate with reduction asthmatic symptom scores. This overall applied in responders and poor responders of AMP-BPT and His-BPT., Conclusion: Despite higher screening capacity of well-controlled asthma, AMP-BPT confers similar diagnostic performance and safety with His-BPT. AMP-BPT might not preferentially reflect changes asthmatic symptoms., (© 2015 John Wiley & Sons Ltd.)

Background: Little information exists on whether gender or asthma status modifies the effects of secondhand smoke (SHS) exposure on lung function., Objective: To evaluate whether gender or asthma status modifies the association of SHS exposure with lung function., Methods: A total of 6,740 children (average 11.6 years) were recruited from 24 districts of 7 cities in northeast China in 2012. SHS exposure included exposure to environmental and maternal smoking both in utero and during early childhood (postnatal). Lung function was measured using electronic spirometers. Two-step regressions were used to analyze the association between SHS and lung function., Results: In utero and postnatal exposure to SHS was independently associated with decreased lung function in both genders; however, this association was greater among males. For example, when exposed to maternal smoking during pregnancy, the adjusted odds ratio (aOR) for decreased forced vital capacity (FVC) was 6.46 (95% confidence interval [CI]: 2.58-16.17) among males, while only 2.16 (95% CI: 0.96-4.88) among females. More positive associations between SHS exposure and decreased lung function were detected among nonasthmatic compared with asthmatic children. Nonasthmatics had significantly larger deficits from in utero exposure to maternal smoking, which concerned decreased lung FVC function (aOR = 2.58, 95% CI: 1.28-5.21) and decreased lung forced expiratory volume in 1 s (FEV1) function (aOR = 2.32, 95% CI: 1.01-5.33). A similar pattern was also observed for the associations between SHS exposure and continuous pulmonary function test measurements., Conclusions: SHS exposure was associated with decreased lung function. Males and nonasthmatics seem to be more susceptible than their respective counterparts., (© 2017 S. Karger AG, Basel.)

Objective: To investigate the characteristics of lower airway abnormalities in allergic rhinitis(AR) patients without asthma. Methods: Between June 2008 and December 2012, 377 consecutive AR patients and 264 healthy subjects were recruited. All subjects underwent meticulous history taking, nasal examination, allergen skin prick test, blood routine test, serum total immunoglobin E assay, induced sputum cell count and differentials, measurement of fractional exhaled nitric oxide (FeNO) and bronchial challenge test. Results: The positive rates in AR patients was 12.2%(46/377) for bronchial provocation test, 49.2%(185/377) for FeNO, 39.0%(147/377) for sputum eosinophilia, 15.6%(40/377) for peripheral blood eosinophilia and 55.4%(209/377) for increased serum total IgE levels, which were consistently and statistically higher than those of healthy controls( P <0.01). The levels of FeNO [35.0 (21.8, 65.9)ppb], induced sputum eosinophil percentage [2.0 (0.0, 7.5)%], peripheral blood eosinophil percentage [2.9 (1.8, 4.5)%] and serum total IgE [178.4 (63.1, 384.0)kU/L] in AR patients were also higher( P <0.01). Compared with healthy controls, patients with AR demonstrated lower levels of FEV 1 /FVC%, MMEFpred%, MEF 75 pred%, MEF 25 pred% (all P <0.05). Statistical analysis showed that FeNO, ratio of induced sputum eosinophil percentage and peripheral blood eosinophil percentage had significant correlations with each other( P <0.01), the r value being 0.247, 0.235, 0.355 respectively. Conclusion: AR without asthma is characterized by lower airway inflammation, small airway impairment and bronchial hyperreactivity, features similar to those of asthma.

Background and Aims: Correlation between fractional exhaled nitric oxide (FeNO) and responsiveness to inhaled leukotriene D4 (LTD4 ) and methacholine (MCh) might be different. This study aims to determine the correlation between FeNO and airway responsiveness to LTD4 and MCh, and to compare the airway responsiveness to inhaled LTD4 and MCh and FeNO in non-smokers, patients without rhinitis and non-smokers without rhinitis., Methods: In this cross-over study, asthmatic patients and healthy subjects underwent LTD4 and MCh inhalation challenge at a 2- to 14-day interval. The FeNO was measured by using NIOX MINO, a portable instrument, at the initial visit, before spirometry and inhalation challenge tests. Subgroup analyses were performed in asthmatic patients based on the categorisation of never-smoker group, non-rhinitis group and never-smoker without rhinitis group., Results: Of 62 asthmatic patients enrolled, 43 did not have self-reported rhinitis (asthmatic patients without rhinitis), 56 were never-smokers (asthmatic non-smokers), giving rise to 37 non-smokers who did not have rhinitis (asthmatic non-smokers without rhinitis). Twenty-one healthy subjects were enrolled. Overall, Log10 FeNO correlated with Log10 PD20 FEV1 -MCh but not Log10 PD20 FEV1 -LTD4 or Log10 (LTD4 /MCh potency ratio). Reduced FeNO was associated with significantly higher Log10 PD20 FEV1 -MCh but not Log10 PD20 FEV1 -LTD4 , except for non-smokers. Compared with all asthmatic patients, asthmatic non-smokers without rhinitis were characterised by markedly reduced levels of Log10 PD20 FEV1 -MCh but not Log10 PD20 FEV1 -LTD4 . The difference in all parameters did not reach statistical significance among asthmatic patients without rhinitis, asthmatic non-smokers and asthmatic non-smokers without rhinitis., Conclusion: FeNO correlates with airway responsiveness to inhaled MCh but not LTD4 , in asthmatic patients, particularly in asthmatic non-smokers without rhinitis., (© 2014 John Wiley & Sons Ltd.)

Introduction: The convenient measure to predict efficacy of leukotriene receptor antagonist is lacking., Objectives: To determine if leukotriene D4 inhalation challenge predicts short-term efficacy of montelukast in asthma., Methods: In this open-labelled 28-day trial, 45 patients with asthma were allocated to leukotriene-sensitive and leukotriene-insensitive group to receive montelukast monotherapy (10 mg, once daily) based on the positive threshold of leukotriene D4 inhalation challenge test (4.800 nmol). Miscellaneous measurements comprised fractional exhaled nitric oxide, methacholine inhalation challenge, Asthma Control Test and Asthma Quality of Life Questionnaire. Peak expiratory flow was self-monitored throughout the treatment. End point assessments were performed 3 to 5 days after montelukast withdrawal., Results: Twenty-three patients in leukotriene-sensitive group and 10 leukotriene-insensitive group completed the study. Both groups differed neither in 28-day peak expiratory flow rate nor in maximal weekly peak expiratory flow (both P > 0.05). However, minimal weekly peak expiratory flow was significantly higher in leukotriene-insensitive group throughout the treatment course (all P < 0.05) except for week 1 (P > 0.05). Both groups did not differ statistically in the post-treatment improvement in forced expiratory volume in 1 s (FEV1 ) predicted% prior to inhalation challenge, fractional exhaled nitric oxide or the airway responsiveness to leukotriene D4 or methacholine (all P > 0.05). There was a marked increase in Asthma Control Test score and the symptom score of Asthma Quality of Life Questionnaire in both groups (both P < 0.05). The overall significance of Logistic regression model was unremarkable (P = 0.467)., Conclusion: Responsiveness to inhaled leukotriene D4 alone might not be sufficient to predict the short-term efficacy of montelukast monotherapy in patients with asthma., (© 2014 John Wiley & Sons Ltd.)

Background: Response-dose ratio (RDR) and cumulative provocative dosage (PD) are useful indices reflecting airway responsiveness in asthma., Objectives: To compare the diagnostic value of RDR and PD, by conducting leukotriene D4 (LTD4-BPT) and methacholine bronchial provocation test (MCh-BPT), in different asthma control levels., Methods: Healthy subjects and asthmatic patients underwent LTD4-BPT and MCh-BPT, at 2-14-day interval. This entailed assessment of the distribution characteristics, correlation, and diagnostic value of PD inducing 20% fall in forced expiratory volume in one second (PD20FEV1) and the RDR, defined as FEV1 fall (%) at the final step divided by the corresponding provocative dosage., Results: Twenty uncontrolled, 22 partly controlled, 20 controlled asthmatics, and 21 healthy subjects were enrolled. Log10RDR was positively correlated with log10PD20FEV1 in both BPTs (all P < 0.05). Poorer asthma control was associated with significantly lower PD20FEV1 and higher RDR (both P < 0.05). The differences in PD20FEV1 and RDR between partly controlled and controlled asthma were unremarkable (both P > 0.05). Compared with log10PD20FEV1, the log10RDR yielded similar diagnostic values in both BPTs. A lower percentile of RDR (≤ 25th percentile) was associated with higher baseline FEV1 (P < 0.05) and an increased proportion of well-controlled asthmatic patients. The combination of RDR and PD20FEV1 led to an increased diagnostic value compared with either parameter alone., Conclusions: RDR is a surrogate of PD20FEV1 for BPTs in asthma. This finding was not modified by different asthma control levels or the types of bronchoprovocants.

Background: The value of impulse oscillometry (IOS) for bronchial provocation testing is poorly defined. We investigated the positive threshold derived from the parameters and diagnostic power of IOS for asthma with the leukotriene D(4) bronchial provocation test., Methods: We enrolled 62 subjects with asthma and 21 healthy subjects. IOS was employed to perform the leukotriene D(4) bronchial provocation test, followed by spirometry. The positive threshold was determined based on the cutoff point in the receiver operating characteristic curve, from which the parameters with the highest diagnostic power were obtained., Results: Airway impedance at 5 Hz (Z(5)), resistance at 5 Hz (R(5)), and resonance frequency had the highest diagnostic power (areas under curve 0.82, 0.82, and 0.81, respectively), with increases of 57%, 43%, and 63%, corresponding to a 20% decrease in FEV(1), respectively. IOS indices yielded assay sensitivity and specificity similar to that of spirometry. The positive threshold for IOS, defined as either a 57% increase in Z(5) or a 63% increase in resonance frequency in the bronchial provocation test, yielded an assay accuracy of 0.6 in subjects with asthma., Conclusions: IOS during the leukotriene D(4) bronchial provocation test has a diagnostic power similar to that of spirometry. Either a 57% increase in Z(5) or a 63% increase in resonance frequency may be regarded as a surrogate of FEV(1) decrease to determine airway hyper-responsiveness in asthma.