Jiaying An

Leukotriene D4 and methacholine bronchial provocation tests for identifying leukotriene-responsiveness subtypes

BACKGROUND Both leukotriene D(4) (LTD(4)) and methacholine bronchial provocation tests are measurements of airway responsiveness; however, their correlation and distinction remain unexplored. OBJECTIVES We sought to compare the 2 tests and classify leukotriene-responsiveness subtypes in asthmatic patients. METHODS In this randomized cross-over study we enrolled healthy subjects and asthmatic patients with different control statuses. All subjects underwent both tests with a 2- to 14-day interval. Distribution and correlation of cumulative doses inducing a 20% decrease in FEV(1), LTD(4)/methacholine potency ratio, diagnostic value, and adverse events were recorded and analyzed. Asthmatic patients with a lower cumulative dose for LTD(4) and a higher leukotriene/methacholine potency ratio than geometric means were regarded as leukotriene responsive. RESULTS Twenty patients with uncontrolled, 22 with partly controlled, and 20 with controlled asthma and 21 healthy subjects were enrolled. Geometric means of cumulative doses for LTD(4) and methacholine (0.272 nmol vs 0.945 μmol) were lowest in patients with uncontrolled asthma, followed by those with partly controlled (0.387 nmol vs 1.933 μmol) and controlled (1.484 nmol vs 3.946 μmol) asthma. The average potency ratio was highest in those with partly controlled asthma (5000.2), followed by those with uncontrolled (3477.7) and controlled (2702.6) asthma. Eighteen leukotriene-responsive asthmatic patients (29.03%) with a cumulative dose of LTD(4) of 0.533 nmol or less and a potency ratio of 3647 or greater were identified. Adverse events, including tachypnea and chest tightness, were similar and mild. No serious adverse event was reported. CONCLUSION Diagnostic value and safety were ideal in both tests. The combination of cumulative dose for LTD(4) and potency ratio might be useful to identify leukotriene-responsive asthmatic patients.

Leukotriene D4 bronchial provocation test: methodology and diagnostic value

Abstract Background: Although leukotriene D4 (LTD4) is a potent bronchoconstrictor, little is known about airway responsiveness to LTD4 in asthmatics with different inflammation phenotypes. Objectives: To establish the methodology and investigate the distribution characters of airway responsiveness, diagnostic value and safety of LTD4 bronchial provocation test. Methods: LTD4 bronchial provocation tests were performed in 62 asthmatics and 21 normal controls. Airway responsiveness was assessed based on the cumulative dosage causing a 20% fall in FEV1 (PD20FEV1-LTD4) and was expressed as (median, interquartile range). The fall in spirometric parameters was plotted showing the distribution characters. The diagnostic value was assessed using receiver operation characteristic (ROC) curve. All adverse events were recorded during the test. Results: Airway responsiveness to LTD4 was significantly higher in asthmatics (0.410 nmol, 0.808 nmol) as compared with normal controls (5.00 nmol, 0.00 nmol). The decrease in spirometric parameters varied after bronchoprovocation, which was negatively correlated with PD20FEV1-LTD4, among which FEV1 had a maximal slope (r = −0.524, P = 0.000). High diagnostic value (AUC: 0.914, 95%CI: [0.855, 0.974]) was revealed by ROC curve. The major adverse events were dyspnea (82.3%), chest tightness (72.6%), wheezing (32.3%) and coughing (25.8%) in asthmatics, which could overall be recovered within 15.0 minutes after inhalation of 200 ∼ 400 mcg salbutamol MDI. No serious adverse event was reported. Conclusion: The established procedure of LTD4 bronchial provocation test is effective in the diagnosis of asthma and is well tolerated. Future studies are necessary to provide more evidences in terms of safety and efficacy. This may be helpful upon further application in clinical practice.

Responsiveness to leukotriene D 4 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.

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

The convenient measure to predict efficacy of leukotriene receptor antagonist is lacking.

What is the difference between FEV1 change in percentage predicted value and change over baseline in the assessment of bronchodilator responsiveness in patients with COPD

BACKGROUND Several criteria are clinically applied in the assessment of significant bronchodilator responsiveness in chronic obstructive pulmonary disease (COPD). The present study aimed to investigate the differences in various degree of severity of COPD among these criteria. METHODS After 400 micrograms of salbutamol administered via spacer by metered dose inhaler (MDI), forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) changes (including percentage change, absolute change and absolute change in percentage predicted value) were retrospectively analysed in 933 stable patients with mild-to-very-severe COPD. Significant bronchodilator responsiveness was assessed using American Thoracic Society and European Respiratory Society (ATS-ERS) criterion based on FEV1 or/and FVC (both ≥12% increase over baseline and ≥200 mL) and FEV1 percentage predicted criterion (≥10% absolute increase in percentage predicted FEV1) in different grades of COPD. RESULTS Of the patients [age 66.8 years, baseline FEV1 974 mL (39.3% predicted) and FVC 2,242 mL], mean improvements were 126 mL in FEV1 and 265 mL in FVC; 21.4% and 45.3% met ATS-ERS criterion based on FEV1 and FVC, respectively; and 13.5% met FEV1 percentage predicted criterion. The responsive ratios of ATS-ERS criterion based on FEV1 to FEV1 percentage predicted criterion in grade I, II, III and IV of COPD were 0.95(:)1.26(:)2.53(:)6.00, respectively (P<0.01 in grade II and P<0.001 in grade III). As the degree of severity increased, the mean improvement of FEV1 was reduced; on the contrary, that of FVC was increased. CONCLUSIONS Compared with FEV1 percentage predicted criterion, ATS-ERS criterion based on FEV1 as well as FVC, the later in particular, detected a larger percentage of patients with significant responsiveness. The increasing difference was relevant as a function of the severity of airflow obstruction.

Adenosine monophosphate is not superior to histamine for bronchial provocation test for assessment of asthma control and symptoms

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.

Vibration response imaging in idiopathic pulmonary fibrosis: a pilot study.

BACKGROUND: Vibration response imaging (VRI) is a novel imaging technique and little is known about its characteristics and diagnostic value in idiopathic pulmonary fibrosis (IPF). The aim of this study was to investigate the features of VRI in subjects with IPF. METHODS: We enrolled 23 subjects with IPF (42–74 y old) and 28 healthy subjects (42–72 y old). Subjects with IPF were diagnosed by lung biopsy and underwent VRI, spirometry, lung diffusion testing, and chest x-ray or computed tomography, which entailed assessment of the value of VRI indices. RESULTS: The total VRI score correlated statistically with single-breath carbon monoxide diffusing capacity percent predicted (r = −0.30, P = .04), but not with FVC percent predicted, FEV1 percent predicted, and FEV1/FVC (r = −0.27, −0.22, and 0.19; all P > .05). Compared with healthy subjects (17.9%), 20 subjects with IPF (86.96%, P < .01) presented with significantly increased crackles. The difference in quality lung data in all lung regions was unremarkable (all P > .05), except for the upper right and lower left lobes (P < .05). Overall, VRI parameters yielded acceptable assay sensitivity and specificity. Maximum energy frame was characterized by the highest diagnostic value (sensitivity, 1.00; specificity, 0.82), followed by presence of abundant crackles (sensitivity, 0.70; specificity, 0.96). Total VRI score was not a sensitive indicator of IPF, owing to low assay sensitivity (0.70) and specificity (0.64). CONCLUSIONS: VRI may be helpful to discriminate between IPF subjects and healthy individuals. Maximum energy frame and abundant crackles might serve as a diagnostic tool for IPF.