Responsiveness to methacholine, but not leukotriene D4, correlates with fractional exhaled nitric oxide in 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.

Leukotriene D4 inhalation challenge for predicting short-term efficacy of montelukast: a pilot study.

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.

Response--dose ratio is a surrogate of cumulative provocative dosage for bronchial provocation tests in asthma.

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.

[Single-breath and rebreathing methods for measurement of pulmonary diffusing function: a comparative study].

OBJECTIVE: To compare the difference of pulmonary diffusing capacity measured by single-breath (SB) and re-breathing (RB) in normal subjects, patients with interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD). METHODS: We enrolled a cohort of subjects from the Guangzhou Institute of Respiratory Disease between September 2011 and February 2012: control group 29 (male 9, female 20, 42-74 y), ILD group 32 (male 15, female 17, 41-72 y), COPD group 32 (male 28, female 4, 40-75 y). All subjects underwent pulmonary diffusing capacity test using SB or RB method according to random figures order list. Diffusing capacity of carbon monoxide per predicted measured by SB method (SB-DLCO%pred) of the normal group was used as the standard to adjust the diffusing capacity of carbon monoxide per predicted measured by RB method (RB-DLCO%pred) and diffusing capacity of carbon monoxide per liter of VA per predicted measured by RB (RB-DLCO/VA%pred) in the 3 groups, respectively. Comparisons between 2 groups were performed by using the independent-sample t test, among more than 2 groups by using the One-Way ANOVA test, while the ROC curve was used to calculate the area under curve (AUC) and its 95%CI. RESULTS: In the control group, 15 subjects' RB-DLCO%pred was lower than 80%, and the mean value (78.8 ± 2.1)% was also lower than 80%. Using SB-DLCO%pred of the normal group as a standard to adjust the RB-DLCO%pred, the corrected value was 1.097, and then this value was used to adjust RB-DLCO/VA%pred in the 3 groups, respectively. Before correction DLCO%pred [the control group: (91.2 ± 1.9)% vs (78.8 ± 2.1)%; the ILD group: (45.8 ± 2.6)% vs (60.0 ± 1.9)%;the COPD group: (66.3 ± 2.9)% vs (56.6 ± 1.6)%]and DLCO/VA%pred [the control group: (99.8 ± 2.3)% vs (84.6 ± 4.5)%; the ILD group: (75.9 ± 3.0)% vs (88.5 ± 5.4)%; the COPD group: (80.2 ± 3.7)% vs (50.6 ± 2.5)% ] between the SB and RB were statistically different among the 3 groups. After correction, only the DLCO%pred [(45.8 ± 2.6)% vs (65.8 ± 2.1)%], DLCO/VA%pred [ (75.9 ± 3.0)% vs (102.2 ± 6.2)%] of the ILD group and the DLCO/VA%pred [(80.2 ± 3.7) vs (58.3 ± 2.8)%] of the COPD group had significant difference between the 2 methods (t = -6.00-4.68, all P < 0.01) . The test time of re-breathing in the COPD group (106 ± 5) s was significant longer than that of the ILD group (73 ± 4) s and the control group (79 ± 5) s (F = 11.99, P < 0.01), and the correlation between DLCO/VA%pred and the test time(r = -0.661, P < 0.01) was higher than the relationship between DLCO%pred and the test time (r = -0.391, P < 0.01). Furthermore, in the ILD group, the area of RB-DLCO%pred under ROC was 0.893, 95%CI being 0.817-0.970. In the COPD group, the area of RB-DLCO/VA%pred under ROC was 0.895, 95%CI being 0.811-0.979. CONCLUSIONS: There were differences between re-breathing and single-breath in measuring diffusing capacity. The present predicted value of the re-breathing method needed further study to confirm its applicability. Re-breathing method was more consistent with the respiratory physiology, and might be a better method to detect diseased states.

Responsiveness to leukotriene D4 and methacholine for predicting efficacy of montelukast in asthma.

A lower responsiveness to leukotriene D4 (LTD4) or higher LTD4/[methacholine (MCh)] potency ratio might suggest preferable outcomes of short-term montelukast monotherapy in terms of airway inflammation and lung function in asthmatic patients.

Impulse oscillometry for leukotriene D4 inhalation challenge in asthma.

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.