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.

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.

Emerging electrochemical biosensors for lung cancer-associated protein biomarker and miRNA detection.

Lung cancer remains a major driver of global morbidity and mortality, and diagnosing lung tumors early in their development is vital to maximizing treatment efficacy and patient survival. Several biomarkers, including CYFRA 21-1, NSE, ProGRP, CEA, and miRNA, have been identified as reliable indicators for early lung cancer detection and monitoring treatment progress. However, the minute changes in the levels of these biomarkers during the early stages of disease necessitate advanced detection platforms. In this space, electrochemical biosensors have currently emerged as robust tools for early lung cancer screening and diagnosis owing to their low costs, rapid responses, and superior sensitivity and selectivity. This review provides an up-to-date overview of the application of electrochemiluminescence, photoelectrochemical, and other electrochemical analytical strategies for detecting lung cancer-associated protein biomarkers, and miRNA. This review compares these techniques to provide a concise overview of the principles underlying these electrochemical analytical methods, the preparation of their components, and the performance of the resulting biosensors. Lastly, a discussion of the challenges and opportunities associated with electrochemical biosensors detection of lung cancer-associated biomarkers are provided.

[Research progress in biosensors for adiponectin].

Adiponectin, a cytokine associated with adipose tissue, is a recently defined adipocytokine involved in insulin, glucose, and adipocyte metabolism. Reduced adiponectin levels can increase the risk of developing metabolic syndrome (MS). Adiponectin is considered an important target for the treatment of type 2 diabetes mellitus (T2DM) and MS due to its anti-atherosclerotic and insulin-sensitizing effects. Therefore, the accurate determination of adiponectin concentrations in human plasma is necessary for the management of both T2DM and MS. A variety of biosensors have been developed for the detection of biomarkers such as adiponectin. This paper reviews the applications of electrochemical sensors, surface-enhanced Raman scattering sensors, and microfluidic chip-based chemiluminescence sensors in the detection of adiponectin and the recent research progress in the sensors for the detection of adiponectin, aiming to provide a reference for the research and application of sensors for adiponectin in the medical field.

[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.

Body mass index affects spirometry indices in patients with chronic obstructive pulmonary disease and asthma.

Background: Body mass index (BMI) is known to affect the outcomes of spirometry indices. However, its association with spirometry indices in COPD and asthma is less studied. We aimed to explore the impact of BMI on these patients. Methods: Patients with COPD or asthma who completed bronchodilator tests (BDTs) between 2017 and 2021 were reviewed. Spirometry indices were compared among patients with COPD or asthma that were subclassified as underweight (BMI< 18.5 kg/m2), normal weight (≥18.5 to < 25), overweight (≥ 25 to < 30), and obesity (≥ 30). Results. Results: Analysis was conducted on 3891 COPD patients (age:66.5 ± 7.8 years) and 1208 asthma patients (age:59.7 ± 7.5 years). COPD patients classified as underweight demonstrated significantly lower values of pre-and post FEV1 (L, %), pre-and post FVC (L, %), and pre- and post-FEV1/FVC (all p < 0.05). In contrast, COPD patients who were overweight or obese exhibited higher values for pre-and post FEV1 (L, %), and pre and post FEV1/FVC (all p < 0.05). Within the cohort of asthma patients, those underweight had lower pre-and post FEV1 (L, %), pre and post FVC (L, %), pre and post FEV1/FVC %. Obese asthma patients displayed higher pre and post FEV1/FVC (all p < 0.05). Conclusion: Significant BMI category differences in spirometry indices can be seen in patients with COPD or asthma. Both underweight and obesity could affect the diagnosis and severity of these diseases. Recognizing these effects is essential to better management and diagnosis of these patients.

Two-minute tidal breathing methacholine bronchial challenge: Comparison of two jet nebulisers.

BACKGROUND: The American Thoracic Society (ATS) guideline for methacholine challenge testing (MCT) recommended using the English Wright (EW) nebuliser. However, other brands of nebulisers are also indicated to be acceptable for this technique, but further validation of nebuliser performance is recommended. OBJECTIVE: To compare the methacholine provocation concentration causing a 20% fall in forced expiratory volume in 1 second (PC20 -FEV1 ) measured by using EW nebuliser and DV 646 nebuliser. METHODS: Subjects were randomly assigned to undergo 2-min tidal breathing methacholine challenge with either EW or DV 646 nebuliser on two separate days, which were at least 24 hours but not more than 7 days apart. The above procedure was repeated for each subject in 1 month, but the nebulisers were selected in a reverse order. RESULTS: The study includes 15 mild and stable asthmatic patients. The geometric means (SD) of methacholine PC20 measured with using EW and DV 646 nebulisers were 1.82 (6.38) mg/mL versus 0.83 (1.82) mg/mL, respectively in the initial two visits and 2.56 (6.29) mg/mL versus 0.78 (1.40) mg/mL in the following two visits (both P < 0.05). There are well correlations between PC20-EW1 and PC20-EW2 (r = 0.99, P < 0.01), PC20-DV1 and PC20-DV2 (r = 0.88, P < 0.01), and between PC20-EW1 and PC20-DV1 (r = 0.91, P < 0.01), PC20-EW2 and PC20-DV2 (r = 0.78, P < 0.01). CONCLUSIONS: PC20 -FEV1 measured by using the two conventional jet nebulisers was both repeatable and the results were highly correlated.

Response of upper and lower airway inflammation to bronchial challenge with house dust mite in Chinese asthmatics: a pilot study.

BACKGROUND: Allergen nasal challenge can induce increase of eosinophils in sputum, but report about eosinophilic inflammation in upper airway after allergen bronchial challenge in Chinese asthmatics was rare. The article aims to evaluate response of upper and lower airways to house dust mite (HDM) allergen bronchial challenge. METHODS: HDM allergen bronchial challenge was carried out in asthmatic patients with allergic rhinitis (AR). Bronchial methacholine challenge and blood test were performed before and at 24 hours after allergen challenge. Nasal lavage and induced sputum for differential cells count and fractional exhaled nitric oxide (FeNO) measurement were performed before, 7 and 24 hours after allergen challenge. RESULTS: Eighteen asthmatic patients with AR underwent HDM allergen bronchial challenge with no serious adverse events reported. Fifteen patients showed dual asthmatic response (DAR), while 2 patients showed early (EAR) and 1 late asthmatic response (LAR) only. At 24 hours after allergen bronchial challenge testing, average PC20FEV1 to methacholine significantly decreased (1.58 to 0.81 mg/mL, P=0.03), while both FeNO and the percentage of eosinophils in blood and sputum were significantly increased [52.0 (54.0) to 69.0 (56.0) ppb, P=0.01; 4.82% to 6.91%, P<0.001; 20.70% to 27.86%, P=0.03, respectively], but with no significant differences found in the percentage of eosinophils in nasal lavage (39.36% to 38.58%, P=0.89). However, at 7 hours after allergen challenge, the eosinophils in sputum were significant increased to 40.45% (P<0.001), but there was an increase (39.36% to 48.07%) with no statistical difference (P=0.167) found in nasal lavage. CONCLUSIONS: HDM allergen bronchial challenge induced different response of airway inflammation in upper and lower airways.

FEF25-75% Is a More Sensitive Measure Reflecting Airway Dysfunction in Patients with Asthma: A Comparison Study Using FEF25-75% and FEV1.

BACKGROUND: Reduced forced expiratory flow between 25% and 75% of vital capacity percent predicted (FEF25-75%) representing small airway dysfunction (SAD) was associated with asthma development and progression. OBJECTIVE: To investigate whether FEF25-75% was superior to forced expiratory volume in 1 second in predicted (FEV1%) in reflecting asthma features in adult patients. METHODS: A retrospective spirometry dataset comprising 1801 adult patients with confirmed asthma and a subgroup of 332 patients having detailed clinical data were used to explore the association of FEF25-75% and/or FEV1% with clinical features of asthma. RESULTS: Of the 1801 subjects, FEV1% and FEF25-75% ranged from 136.8% to 10.2% and 127.3% to 3.1%, respectively. FEF25-75% < 65% was present in 1,478 (82.07%) of patients. FEF25-75% was strongly correlated with matched FEV1% (r = 0.900, P < .001). FEF25-75% and FEV1% were both correlated with airway hyperresponsiveness (r = 0.436, P < .001; r = 0.367, P < .001), asthma control test score (r = 0.329, P < .001; r = 0.335, P < .001), and sputum eosinophil count (r = -0.306, P < .001; r = -0.307, P < .001). Receiver-operating characteristic curves showed that FEF25-75% had greater value in predicting severe asthma (area under the curve: 0.84 vs 0.81, P = .018), airflow obstruction (0.97 vs 0.89, P < .001), and severe bronchial hyperresponsiveness (0.74 vs 0.69, P = .012) as compared with FEV1%. Patients with SAD (FEF25-75% < 65%) in the presence of normal FEV1% exhibited higher sputum eosinophil counts and had an increased dosage of daily inhaled corticosteroids (P < .001 and P = .010) than patients with normal lung function and their FEF25-75% values correlated with sputum eosinophil count (r = -0.419, P = .015), but not FEV1%. CONCLUSION: FEF25-75% represented small airway function and was more sensitive at reflecting airway hyperresponsiveness, inflammation, and disease severity as compared with FEV1% in patients with asthma. Our data suggest further assessment of FEF25-75% in asthma management, particularly for those with SAD who present normal FEV1%.

[Investigation on quality of spirometry in 36 large hospitals in China].

OBJECTIVE: To assess the current status of quality control of spirometry reports in China. METHODS: Spirometry case reports from January 2008 to October 2008 were collected from pulmonary function testing laboratories in 36 large hospitals (provincial or municipal) in China. The quality analysis was performed according to ATS/ERS standardization for measurement of spirometry. The number of reports that met the criteria for quality control was expressed as percentages. RESULTS: A total of 345 spirometry test reports were collected. 82.5% (282/342) met the start-of-test criteria for quality control. 333 reports could be analyzed for free of artifacts, of which 65.8% (219/333) were consistent with the criteria of smooth expiration; the remaining reports (114) failed to meet the criteria, for reasons including cough (29/333, 8.7%), premature glottis closure (8/333, 2.4%), gas leakage (29/333, 8.7%), early termination of expiration (26/333, 7.8%), mouthpiece obstruction (6/333, 1.8%), and incomplete exertion of efforts (49/333, 14.7%). 235 reports were analyzed for end-of-test criteria, with 50.6% (119/235) complying to criteria. 22.6% (78/345) of the reports were tested for more than 3 times, among which 65 reports with the data of each manoeuvre could be analyzed for repeatability. 95.4% (62/65) of the reports met the repeatability criteria, which accounted for 18.0%(62/345)of the total reports collected. The rate of the 2 highest FVC (forced vital capacity) and FEV(1) (forced expiratory volume in one second) of less than 150 ml was 95.4% (62/65) and 100.0% (65/65), respectively. The rate of the 2 highest FVC and FEV(1) of less than 100 ml was 92.3% (60/65) and 87.7% (57/65), respectively. Only 7.2% of the reports (25/345) met all of the 4 criteria listed above. CONCLUSIONS: The quality of spirometry tests in large (provincial or municipal) hospitals in China needs to be improved in the future.

Correction: Mutation spectrums of TSC1 and TSC2 in Chinese women with lymphangioleiomyomatosis (LAM).

[This corrects the article DOI: 10.1371/journal.pone.0226400.].

Methacholine bronchial provocation test for assessment of bronchial hyperresponsiveness in preschool children.

BACKGROUND: Bronchial hyperresponsiveness (BHR) has not been extensively performed in preschool children, possibly because of the difficulty in cooperating with the tests. We sought to determine the usefulness and safety of methacholine bronchial provocation test (MCh-BPT) for BHR assessment in preschool children. METHODS: We recruited 252 preschool children (190 healthy and 62 with wheezing) who underwent MCh-BPT at baseline. MCh-BPT was re-scheduled in case initial attempts failed. Forced expiratory volumes in 0.5 (FEV0.5), 0.75 (FEV0.75) and one second (FEV1) were measured. We recorded the provocative dose causing 15% (PD15) or 20% reduction (PD20) in FEV0.5, FEV0.75 and FEV1, thus allowing for comparison of the diagnostic value of PD15 and PD20. RESULTS: A total of 209 children [156 (82.1%) healthy, 53 (85.5%) with wheezing] successfully completed MCh-BPT. Compared with healthy children, a significantly greater proportion of children with wheezing had measurable PD15FEV0.5, PD15FEV0.75 and PD15FEV1 (P<0.01), and PD20FEV0.5, PD20FEV0.75 and PD20FEV1 (P<0.05). The sensitivity was 92.5% and 94.3% for PD20FEV1, and PD15FEV1 and the specificity was 93.6% and 93.6% respectively, for discriminating asthmatic from healthy children. CONCLUSIONS: Most preschool children successfully and safely complete MCh-BPT, with higher success rate in larger age group. PD20FEV0.5 and PD20FEV0.75 can be surrogates of PD20FEV1 among children whose expiration lasted for less than one second. PD15 has a good diagnostic value as PD20 for diagnosing of BHR in preschool children, which are also more suitable for children five years old or elder.

Mutation spectrums of TSC1 and TSC2 in Chinese women with lymphangioleiomyomatosis (LAM).

The aim of our study was to elucidate the landscapes of genetic alterations of TSC1 and TSC2 as well as other possible non-TSC1/2 in Lymphangioleiomyomatosis (LAM) patients. Sixty-one Chinese LAM patients' clinical information was collected. Tumor biopsies and matched leukocytes from these patients were retrospectively analyzed by next generation sequencing (NGS), chromosomal microarray analysis (CMA), and multiplex ligation-dependent probe amplification (MLPA). Eighty-six TSC1/2 variants were identified in 46 of the 61 LAM patients (75.4%) in which TSC2 and TSC1 variants were 88.37% and 11.63% respectively. The 86 variants are composed of (i) 52 single nucleotide variants (SNVs) (including 30 novel variants), (ii) 23 indels (including 21deletions, and 2 insertions), (iii) a germline duplication of exon 31-42 of TSC2, (iv) a 2.68 Mb somatic duplication containing TSC2, and (v) 9 regions with copy-neutral loss of heterogeneity (CN-LOHs) present only in the LAM patients with single TSC1/2 mutations. Sixty-one non-TSC1/2 variants in 31 genes were identified in 37 LAM patients. Combined applications of different techniques are necessary to achieve maximal detection rate of TSC1/2 variants in LAM patients. Thirty novel TSC1/2 variants expands the spectrum of TSC1/2 in LAM patients. Identification of 61 non-TSC1/2 variants suggests that alternative genes might have contributed to the initiation and progression of LAM.

Absence of relationships between tuberculin responses and development of adult asthma with rhinitis and atopy.

OBJECTIVE: To investigate the relationship between tuberculin skin responses and the development of adult asthma, rhinitis, and atopy. METHODS: Two hundred fourteen patients with mild-to-moderate asthma accompanied with rhinitis and 220 normal volunteers underwent a medical history, chest radiography, allergen skin-prick testing (SPT), bovine Mycobacterium tuberculosis vaccine (BCG) scar identification, purified protein derivative (PPD) tuberculin skin testing, serum-total and serum-specific IgE measurements, and bronchial provocation (provocative dose of histamine causing a 20% fall in FEV(1) [PD(20)]). RESULTS: Thirty-one normal volunteers (14.1%) and 168 asthma-rhinitis subjects (78.5%) had one or more positive skin test results (p < 0.0001). Neither the presence of a BCG scar nor a history of BCG vaccination had a significant effect on atopy in either group. The rate of PPD positivity had no statistical difference between atopy and nonatopy in both groups. In multivariate logistic regression analysis, the odds ratio for tuberculin reactivity was not related to the level of serum-total IgE nor to the level of serum-specific IgE to Dermatophagoides pteronyssinus (DP) and Dermatophagoides farinae (DF), skin response to DP and DF, and PD(20). Overall, no significant correlations were found between tuberculin skin reactivity and log serum-total IgE or PD(20). CONCLUSION: There is no relationship between history of tuberculosis infection, tuberculin responses, and development of adult bronchial asthma, allergic rhinitis, and atopy. Our study suggests that the protection provided by intradermal BCG vaccination in infants to prevent atopic diseases may be limited in early childhood, when a substantial memory of cellular immune modulation still exists.

[Comparison of high-intensity and anaerobic threshold programs in rehabilitation for patients with moderate to severe chronic obstructive pulmonary disease].

OBJECTIVE: To compare two training programs in rehabilitation for patients with moderate to severe chronic obstructive pulmonary disease (COPD). METHODS: Of the 54 patients who entered the study, 41 completed the rehabilitation program. Thirty-two COPD patients were randomly assigned to either the anaerobic threshold group (AT, n = 15) or the high-intensity group (HI, n = 17). Another group was the control group (NT, n = 9). Bicycle exercise training was conducted for 2 days each week for a period of 12 weeks. The HI group received the highest level of intensity that could be tolerated. The AT group received a training intensity corresponding to the anaerobic threshold. Main assessments included lung function test, cardiopulmonary exercise testing, the St George's Respiratory Questionnaire and the Borg dyspnea scale before and after the rehabilitation program. The data of the baseline clinical characteristics of groups were presented as (-x) +/- s. Comparison within two means were analysed through one-sample t test or paired t test. One-way analysis of variance was used to compare multiple means. The rates were analysised by Fish exact probabilities. The Wilcoxon rank sum test was used for comparisons within the groups and the Mann-Whitney u test for intergroup comparisons. RESULTS: Both the AT and HI groups showed significant improvement in Vo(2peak)% pre after rehabilitation, with the former increasing from (61 +/- 11)% to (69 +/- 14)%, and the latter increasing from (72 +/- 12)% to (79 +/- 13)%. The degree of improvement of both groups (AT and HI) were (14 +/- 17)% and (12 +/- 13)%, the difference being not significant (z = -0.180, P > 0.05). At 56 W work rate, the minute ventilation decreased from (36 +/- 4) L/min to (33 +/- 5) L/min (t = 6.167, P < 0.01), the breathing frequency decreased from (32 +/- 1) beats/min to (31 +/- 3) beats/min (t = 2.876, P < 0.05), and the tidal volume increased from (1.2 +/- 0.3) L to (1.3 +/- 0.3) L (t = 2.587, P < 0.05) in the HI group. After rehabilitation the heart rates [(109 +/- 39, 110 +/- 25) beats/min] were significantly lower than those of the baseline [(116 +/- 39, 114 +/- 42) beats/min] respectively in the AT and the HI groups. Oxygen pulse increased significantly from baseline (9.6 +/- 3.7, 8.5 +/- 4.3) ml/beat to (10.4 +/- 4.0, 9.0 +/- 3.2) ml/beat. This level of exertional dyspnea (DeltaBorg/DeltaVo(2)) was significantly improved from (8.6 +/- 3.2, 6.5 +/- 2.6) to (7.4 +/- 2.5, 5.6 +/- 2.4) in both the HI and the AT group (both P < 0.05). The between-group difference for the change in DeltaBorg/DeltaVo(2), however, was not significant (z = -0.378, P > 0.05). CONCLUSIONS: Both the HI and the AT groups had significant improvements in exercise capacity and dyspnea after pulmonary rehabilitation. The degree of improvement in both groups was similar. But the HI group showed significant improvement in the anaerobic threshold and decrease in ventilatory requirement.

[Evaluation of correlation between pulmonary function testing and high resolution computed tomography in pulmonary alveolar proteinosis].

OBJECTIVE: Pulmonary alveolar proteinosis (PAP) is a rare respiratory disorder featured by lipoproteinaceous material accumulation within alveoli. Pulmonary function testing (PFT) and quantitative high resolution computed tomography (HRCT) are used in evaluation of the severity, development and treatment effects of PAP. METHODS: Seventeen patients (10 males, 7 females), aged from 15 to 51 years old, with PAP histopathologically proven by positive periodic acid Schiff reaction were studied in our institute from 2004 to 2007. PFTs and HRCT were performed in all patients. The quantitative parameters of HRCT included total lung volume (TLV), total lung mass (TLM), air-filling lung volume (AFLV), averaged lung density (ALD) and the ratio of air-filling lung volume to total lung volume (AFLV/TLV). The parameters of PFT included forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC, diffusion capacity of carbon monoxide (D(L)CO), the ratio of D(L)CO to alveolar volume (D(L)CO/V(A)), total lung capacity (TLC), residual volume (RV), RV/TLC. A total of 24 dataset of the PFT and HRCT were collected. The correlation and regression between PFTs and HRCT were analyzed. PFT and HRCT parameters were compared before and after treatment with whole lung lavage in 6 of these patients. The data were expressed with mean +/- standard deviation and analyzed with SPSS 13.0 software. RESULTS: Restrictive ventilation function disorder and diffusion function disorder were found in patients with PAP, with more significant decline in D(L)CO (46.1% of predicted and abnormal rate 94.1%). Correlation between PFTs and HRCT parameters were found, with significance in ALD and FVC (r = -0.469, P = 0.021), TLM and FEV1 (r= -0.482, P = 0.017), AFLV/TLV and PEF (r = 0.511, P = 0.011), D(L)CO and D(L)CO/V(A) (r = 0.659, 0.692, P = 0.000, respectively). The highest correlation was found between D(L)CO/V(A) and AFLV (r = 0.525; P < 0.05). D(L)CO was markedly improved after the treatment of whole lung lavage, simultaneously found with varied improvement of quantitative parameters of HRCT measurements. CONCLUSIONS: Pulmonary function was impaired and correlated with abnormal appearance in HRCT in patients with PAP. Quantitative HRCT may be helpful in prediction of pulmonary function changes. Both techniques are important for the prognosis, outcome and follow-up studies of the disease.

Correlation between upper and lower airway inflammations in patients with combined allergic rhinitis and asthma syndrome: A comparison of patients initially presenting with allergic rhinitis and those initially presenting with asthma.

Allergic rhinitis (AR) and asthma often coexist. The terminology combined allergic rhinitis and asthma syndrome (CARAS) was introduced to describe patients with combined AR and asthma. The aim of the present study was to evaluate the correlation between eosinophilic inflammation in the upper and lower airways of patients with CARAS. Stable patients with CARAS initially presenting with AR or asthma were recruited. Healthy subjects and patients with AR alone were recruited as controls. Clinical characteristics, including disease history, lung function, nasal airway inspiratory resistance and upper and lower airway eosinophilic inflammation were evaluated and compared. A total of 73 subjects (22 patients with CARAS initially presenting with AR, 15 patients with CARAS initially presenting with asthma, 25 patients with AR alone and 11 healthy subjects) were studied. The nasal symptoms visual analogue scale scores at the week prior to enrollment and nasal airway inspiratory resistances were comparable among the groups. The percentage of predicted forced expiratory volume in 1 sec and percentage of predicted maximal middle expiratory flow in patients with CARAS initially presenting with asthma were significantly lower compared with the other three groups (P<0.05). No significant different in the percentage of eosinophils in the nasal lavage was observed between patients with CARAS and those with AR only; however, it was significantly increased compared with healthy subjects (P<0.05). The fractional concentration of exhaled nitric oxide and percentage of eosinophils in the sputum were significantly increased in patients with CARAS compared with those in the AR only and healthy subject groups (P<0.05). The difference in the percentage of eosinophils in the nasal lavage and sputum between patients with CARAS initially presenting with AR and initially presenting with asthma was not significant; however, a positive correlation between the percentage of eosinophils in the upper and lower airways was present in patients with CARAS initially presenting with AR only (r=0.526, P=0.030).

[Evaluation of exercise intensity for pulmonary rehabilitation in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To investigate proper methods and parameters of exercise intensity in pulmonary rehabilitation for patients with chronic obstructive pulmonary disease (COPD). METHODS: Symptom-limited cardiopulmonary exercise test (CPET) was performed in 30 male patients with moderate to severe COPD by cycle ergometer. Exercise intensity parameters, including the measured heart rate reserve (HRR%meas), the predictive heart rate reserve (HRR%pred) and the Borg scale were obtained. The distribution of these parameters ranged from 10% to 90% VO2max were compared. Multiple regression analysis was applied to analyze the relationship among heart rate (HR), the Borg scale and VO2max%. RESULTS: The HRR%meas was close to VO2max%. The coefficient of variation (CV) of HRR%meas was larger than HRR%pred. The larger was the Borg scale, the smaller was the distribution of VO2max%. While the Borg scale were 3, 4, and 5, the exercise intensity achieved 60%, 72%, and 78% VO2max, respectively. Predicted equation (VO2max%=1.026xHR+27.688xBorg-0.179xHRxBorg-63.313, r=0.920, P=0.00) was obtained. CONCLUSION: HRR%meas was a better parameter than HRR%pred for prescribing the exercise intensity. The Borg scale is a simple and applicable method to prescribe and monitor the exercise intensity. It is suggested that Borg scale should reach 4 (moderate dyspnea) in pulmonary rehabilitation for the male patients with moderate to severe COPD. Predicted equation for VO2max% is recommended for monitoring the exercise intensity.

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

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% FEV1 fall (PD20 FEV1 ), diagnostic performance and adverse events (AEs) were compared. Patients with PD20 FEV1 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 PD20 FEV1 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 PD20 FEV1 -AMP and PD20 FEV1 -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.

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.