Yong-hua Gao

Aetiology of bronchiectasis in Guangzhou, southern China.

Aetiologies of bronchiectasis in mainland China and their comparisons with those in western countries are unknown. We aimed to investigate bronchiectasis aetiologies in Guangzhou, southern China, and to determine ethnic or geographic differences with reports from western countries.

Characterization of Lung Function Impairment in Adults with Bronchiectasis

Background Characteristics of lung function impairment in bronchiectasis is not fully understood. Objectives To determine the factors associated with lung function impairment and to compare changes in spirometry during bronchiectasis exacerbation and convalescence (1 week following 14-day antibiotic therapy). Methods We recruited 142 patients with steady-state bronchiectasis, of whom 44 with acute exacerbations in the follow-up were included in subgroup analyses. Baseline measurements consisted of chest high-resolution computed tomography (HRCT), sputum volume, purulence and bacteriology, spirometry and diffusing capacity. Spirometry, but not diffusing capacity, was examined during acute exacerbations and convalescence. Results In the final multivariate models, having bronchiectasis symptoms for 10 years or greater (OR = 4.75, 95%CI: 1.46–15.43, P = 0.01), sputum culture positive for Pseudomonas aeruginosa (OR = 4.93, 95%CI: 1.52–15.94, P<0.01) and HRCT total score being 12 or greater (OR = 7.77, 95%CI: 3.21–18.79, P<0.01) were the major variables associated with FEV1 being 50%pred or less; and the only variable associated with reduced DLCO was 4 or more bronchiectatic lobes (OR = 5.91, 95%CI: 2.20–17.23, P<0.01). Overall differences in FVC and FEV1 during exacerbations and convalescence were significant (P<0.05), whereas changes in other spirometric parameters were less notable. This applied even when stratified by the magnitude of FEV1 and DLCO reduction at baseline. Conclusion Significant lung function impairment should raise alert of chest HRCT abnormality and sputum culture positive for Pseudomonas aeruginosa, in patients with predominantly mild to moderate steady-state bronchiectasis. Acute exacerbations elicited reductions in FVC and FEV1. Changes of other spirometric parameters were less significant during exacerbations. Trial Registration ClinicalTrials.gov NCT01761214

The Relationship between Depression and Asthma: A Meta-Analysis of Prospective Studies.

Background Previous studies have suggested that asthmatic patients often have comorbid depression; however, temporal associations remain unclear. Objectives To determine whether depression predicts asthma and, conversely, whether asthma predicts depression. Methods A literature search was conducted without language restrictions using Pubmed, Embase, Cochrane and PsycINFO for studies published before January, 2015. Papers referenced by the obtained articles were also reviewed. Only comparative prospective studies with reported risk estimates of the association between depression and asthma were included. In order to investigate whether one of these conditions was predictive of the other, studies were excluded if enrolled participants had pre-existing depression or asthma. A random-effects model was used to calculate the pooled risk estimates for two outcomes: depression predicting asthma and asthma predicting depression. Results Seven citations, derived from 8 cohort studies, met our inclusion criteria. Of these, six studies reported that depression predicted incident adult-onset asthma, including 83684 participants and 2334 incident cases followed for 8 to 20 years. Conversely, two studies reported that asthma predicted incident depression. These studies involved 25566 participants and 2655 incident cases followed for 10 and 20 years, respectively. The pooled adjusted relative risks (RRs) of acquiring asthma associated with baseline depression was 1.43 (95% CI, 1.28–1.61) (P<0.001). The adjusted RRs for acquiring depression associated with baseline asthma was 1.23 (95% CI, 0.72–2.10) (P = 0.45). Conclusions Depression was associated with a 43% increased risk of developing adult-onset asthma. However, asthma did not increase the risk of depression based on limited studies. Further prospective studies ascertaining the true association between asthma and subsequent risk of depression are warranted.

Impulse oscillometry in adults with bronchiectasis.

RATIONALE The usefulness of impulse oscillometry (IOS) in bronchiectasis has not been systematically investigated. OBJECTIVES To determine the usefulness of IOS parameters and their correlation with radiology, disease severity, sputum bacteriology, and spirometry, and to compare the changes in IOS parameters during exacerbations and convalescence of bronchiectasis. METHODS We recruited 100 patients with bronchiectasis and 28 healthy subjects. Receiver operating characteristic curve was plotted to analyze the diagnostic performance of IOS parameters. Chest high-resolution computed tomography (HRCT), Bronchiectasis Severity Index (BSI) assessment, sputum culture, and spirometry were performed. Correlation between IOS parameters and clinical indices was determined using the Spearman model. Changes in IOS parameters, compared with spirometry, during exacerbation were assessed in 16 patients with bronchiectasis. MEASUREMENTS AND MAIN RESULTS IOS parameters (in particular, resonant frequency) could discriminate patients with bronchiectasis from healthy subjects. Higher levels of IOS parameters were associated with Pseudomonas aeruginosa infection, dyshomogeneity, higher BSI and HRCT score, more bronchiectatic lobes, and cystic bronchiectasis (all P < 0.05). All IOS parameters but lung resistance at 5 Hz were positively correlated with the duration of bronchiectasis symptoms, number of bronchiectatic lobes, HRCT total scores, and BSI (all P < 0.05), but not sputum bacterial density (P > 0.05). IOS parameters, but not spirometric parameters, were not statistically different between peripheral and peripheral plus central segment bronchiectasis (all P > 0.05). Increased frequency dependence (higher resonance frequency or reactance area) was more likely to be associated with lower HRCT scores (≤5) than FEV1. Compared with FEV1, any single IOS parameter being abnormal was more common in mild bronchiectasis, particularly in patients with HRCT score of 5 or lower. IOS parameters were not statistically different from baseline to exacerbations and convalescence (all P > 0.05). CONCLUSIONS IOS parameters correlate with clinical indices and could reflect peripheral airway abnormality. An increased number of aberrant IOS parameters signals poorer clinical conditions. Increased frequency dependence might be a sensitive marker of mild bronchiectasis. Any single IOS parameter being abnormal sensitively reflects mild bronchiectasis. IOS parameters do not change significantly during bronchiectasis exacerbations. Clinical Trial registered with www.clinicaltrials.gov (NCT01761214).

Capsaicin cough sensitivity and the association with clinical parameters in bronchiectasis.

Background Cough hypersensitivity has been common among respiratory diseases. Objective To determine associations of capsaicin cough sensitivity and clinical parameters in adults with clinically stable bronchiectasis. Methods We recruited 135 consecutive adult bronchiectasis patients and 22 healthy subjects. History inquiry, sputum culture, spirometry, chest high-resolution computed tomography (HRCT), Leicester Cough Questionnaire scoring, Bronchiectasis Severity Index (BSI) assessment and capsaicin inhalation challenge were performed. Cough sensitivity was measured as the capsaicin concentration eliciting at least 2 (C2) and 5 coughs (C5). Results Despite significant overlap between healthy subjects and bronchiectasis patients, both C2 and C5 were significantly lower in the latter group (all P<0.01). Lower levels of C5 were associated with a longer duration of bronchiectasis symptoms, worse HRCT score, higher 24-hour sputum volume, BSI and sputum purulence score, and sputum culture positive for P. aeruginosa. Determinants associated with increased capsaicin cough sensitivity, defined as C5 being 62.5 µmol/L or less, encompassed female gender (OR: 3.25, 95%CI: 1.35–7.83, P<0.01), HRCT total score between 7–12 (OR: 2.57, 95%CI: 1.07–6.173, P = 0.04), BSI between 5–8 (OR: 4.05, 95%CI: 1.48–11.06, P<0.01) and 9 or greater (OR: 4.38, 95%CI: 1.48–12.93, P<0.01). Conclusion Capsaicin cough sensitivity is heightened in a subgroup of bronchiectasis patients and associated with the disease severity. Gender and disease severity, but not sputum purulence, are independent determinants of heightened capsaicin cough sensitivity. Current testing for cough sensitivity diagnosis may be limited because of overlap with healthy subjects but might provide an objective index for assessment of cough in future clinical trials.

Validation of the Mandarin Chinese version of the Leicester Cough Questionnaire in bronchiectasis

BACKGROUND The Leicester Cough Questionnaire (LCQ) has been validated for assessing cough-specific health status in bronchiectasis. We translated the LCQ into Mandarin Chinese and investigated its validity, reliability and responsiveness. METHODS The LCQ was translated into Mandarin Chinese using the forward-backward translation procedure. A total of 144 out-patients completed the Mandarin Chinese version of the LCQ (LCQ-MC), the Hospital Anxiety and Depression Scale (HADS) and the St Georges Respiratory Questionnaire. Reassessments were performed during exacerbations and at 6 months. Concurrent validation, internal consistency, repeatability and responsiveness were determined. RESULTS Minor cultural adaptations were made to the wording of LCQ-MC. No other difficulties were found during the translation process, with all items easily adapted to acceptable Mandarin Chinese. The questionnaire was not changed in terms of content layout and the order of the questions. In cognitive debriefing interviews, participants reported that the questionnaire was acceptable, relevant, comprehensive and easy to complete. The LCQ-MC showed good concurrent validity, internal consistency and test-retest reliability. Responsiveness was shown by significant changes in LCQ-MC scores between steady state, the first exacerbation and following 2-week antibiotic treatment (both interval changes, P < 0.01) CONCLUSION: The LCQ-MC is a valid, reliable and responsive instrument for determining cough-specific health status in Chinese bronchiectasis patients.

Impact of COPD and emphysema on survival of patients with lung cancer: A meta‐analysis of observational studies

Both COPD and emphysema are associated with an increased incidence of lung cancer, but the impacts of these comorbidities on lung cancer prognosis are still unclear. Herein, we conducted a meta‐analysis to clarify whether the presence of these comorbidities indicates poor survival in patients with lung cancer. A comprehensive search was conducted using PubMed, Embase, Web of Science, ASCO Abstracts and Cochrane library for articles published before 1 June 2015. Papers referenced by the obtained articles were also reviewed. Main outcomes were overall survival (OS) and disease‐free survival (DFS) in patients with lung cancer. Pooled hazard ratio (HR) and 95% confidence intervals (CIs) were calculated using random‐effects models. Subgroup and sensitivity analyses were also conducted. Of 58 full texts reviewed, 26 met our inclusion criteria that were derived from 21 and seven studies examining the impacts of COPD and emphysema on survival of lung cancer, respectively. Meta‐analyses revealed that concomitant COPD was associated with poorer OS (HR, 1.17; 95% CI: 1.10–1.25, n = 20), which was independent of tumour staging, diagnostic criteria of COPD or location, and DFS (HR, 1.52; 95% CI: 1.04–2.23, n = 6) with high heterogeneity (I2 = 78%). The presence of emphysema in patients with lung cancer predicted worse OS (HR, 1.66; 95% CI: 1.25–2.22, n = 7), but not poorer DFS. The presence of COPD and emphysema are robust predictors of poor survival in patients with lung cancer. Early detection of these diseases should be taken into account for lung cancer surveillance and management.

Inflammatory Responses, Spirometry, and Quality of Life in Subjects With Bronchiectasis Exacerbations

BACKGROUND: Bronchiectasis exacerbations are critical events characterized by worsened symptoms and signs (ie, cough frequency, sputum volume, malaise). Objectives: Our goal was to examine variations in airway and systemic inflammation, spirometry, and quality of life during steady state, bronchiectasis exacerbations, and convalescence (1 week following a 2-week antibiotic treatment) to determine whether potentially pathogenic microorganisms, including Pseudomonas aeruginosa, were associated with poorer conditions during bronchiectasis exacerbations. METHODS: Peripheral blood and sputum were sampled to detect inflammatory mediators and bacterial densities. Spirometry and quality of life (St George Respiratory Questionnaire [SGRQ]) were assessed during the 3 stages. RESULTS: Forty-eight subjects with bronchiectasis (43.2 ± 14.2 y of age) were analyzed. No notable differences in species and density of potentially pathogenic microorganisms were found during bronchiectasis exacerbations. Except for CXCL8 and tumor necrosis factor alpha (TNF-α), serum inflammation was heightened during bronchiectasis exacerbations and recovered during convalescence. Even though sputum TNF-α was markedly higher during bronchiectasis exacerbations and remained heightened during convalescence, the variations in miscellaneous sputum markers were unremarkable. Bronchiectasis exacerbations were associated with notably higher SGRQ symptom and total scores, which recovered during convalescence. FVC, FEV1, and maximum mid-expiratory flow worsened during bronchiectasis exacerbations (median change from baseline of −2.2%, −0.8%, and −1.3%) and recovered during convalescence (median change from baseline of 0.6%, 0.7%, and −0.7%). Compared with no bacterial isolation, potentially pathogenic microorganism or P. aeruginosa isolation at baseline did not result in poorer clinical condition during bronchiectasis exacerbations. CONCLUSIONS: Bronchiectasis exacerbations are characterized by heightened inflammatory responses and poorer quality of life and spirometry, but not by increased bacterial density, which applies for subjects with and without potentially pathogenic microorganism isolation when clinically stable. (ClinicalTrials.gov registration NCT01761214.)

Sputum matrix metalloproteinase-8 and -9 and tissue inhibitor of metalloproteinase-1 in bronchiectasis: clinical correlates and prognostic implications.

The triplet of airway infection, inflammation and bronchial wall destruction associated with excessive matrix metalloproteinases (MMP) release and imbalance of tissue inhibitor metalloproteinase‐1 (TIMP‐1) is implicated in bronchiectasis. We sought to determine the associations between sputum MMP (MMP‐8, MMP‐9) and TIMP‐1 and the severity of bronchiectasis; the utility of MMP in predicting risks of future bronchiectasis exacerbations (BE); and the changes in MMP levels during BE.

Six-minute walk test in Chinese adults with clinically stable bronchiectasis: association with clinical indices and determinants

Abstract Background: The profiles of 6-minute walk distance (6MWD) in adults with clinically stable bronchiectasis in Chinese adult patients with bronchiectasis are unclear. Objectives: To delineate the 6MWD by stratification of clinical indices, and to investigate the factors associated with reduced 6MWD in Chinese adults with clinically stable bronchiectasis. Methods: We recruited 141 adult bronchiectasis patients (mean age: 44.3 ± 13.9 years). Demography, radiology, spirometry, diffusing capacity, etiology, sputum bacteriology, modified Medical Research Council dyspnea scale (MMRC) and quality of life were assessed. The safety profile of the measurement was also examined. Results: Lower levels of 6MWD were associated with older age (>50 years), higher HRCT total score, presence of cystic bronchiectasis, bilateral bronchiectasis, reduced diffusing capacity, higher MMRC score, and higher SGRQ scores. Correlation coefficients between 6MWD and spirometry and quality of life scores were different in patients with 6MWD higher and lower than lower limit of normal. DLCO being less than 80% predicted (OR = 3.13, 95% CI: 1.32–7.43, P = 0.01) and MMRC scale between 1 and 4 (OR = 6.42, 95% CI: 2.27–18.18, P < 0.01) were the factors associated with 6MWD being less than the lower limit of normal (80% predicted value). No severe adverse events were reported. Conclusion: The 6MWD could be safely measured in adult patients with bronchiectasis and is poorly associated with clinical parameters. DLCO less than 80% predicted and higher MMRC scale are independent predictors of 6MWD below the lower limit of normal. Our findings will provide a reference for management of bronchiectasis patients in mainland China.