Wei-jie Guan

Impact of air pollution on the burden of chronic respiratory diseases in China: time for urgent action.

In China, where air pollution has become a major threat to public health, public awareness of the detrimental effects of air pollution on respiratory health is increasing-particularly in relation to haze days. Air pollutant emission levels in China remain substantially higher than are those in developed countries. Moreover, industry, traffic, and household biomass combustion have become major sources of air pollutant emissions, with substantial spatial and temporal variations. In this Review, we focus on the major constituents of air pollutants and their impacts on chronic respiratory diseases. We highlight targets for interventions and recommendations for pollution reduction through industrial upgrading, vehicle and fuel renovation, improvements in public transportation, lowering of personal exposure, mitigation of the direct effects of air pollution through healthy city development, intervention at population-based level (systematic health education, intensive and individualised intervention, pre-emptive measures, and rehabilitation), and improvement in air quality. The implementation of a national environmental protection policy has become urgent.

Association between Air Pollutants and Asthma Emergency Room Visits and Hospital Admissions in Time Series Studies: A Systematic Review and Meta-Analysis

Background Air pollution constitutes a significant stimulus of asthma exacerbations; however, the impacts of exposure to major air pollutants on asthma-related hospital admissions and emergency room visits (ERVs) have not been fully determined. Objective We sought to quantify the associations between short-term exposure to air pollutants [ozone (O3), carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), and particulate matter ≤10μm (PM10) and PM2.5] and the asthma-related emergency room visits (ERV) and hospitalizations. Methods Systematic computerized searches without language limitation were performed. Pooled relative risks (RRs) and 95% confidence intervals (95%CIs) were estimated using the random-effect models. Sensitivity analyses and subgroup analyses were also performed. Results After screening of 246 studies, 87 were included in our analyses. Air pollutants were associated with significantly increased risks of asthma ERVs and hospitalizations [O3: RR(95%CI), 1.009 (1.006, 1.011); I2 = 87.8%, population-attributable fraction (PAF) (95%CI): 0.8 (0.6, 1.1); CO: RR(95%CI), 1.045 (1.029, 1.061); I2 = 85.7%, PAF (95%CI): 4.3 (2.8, 5.7); NO2: RR(95%CI), 1.018 (1.014, 1.022); I2 = 87.6%, PAF (95%CI): 1.8 (1.4, 2.2); SO2: RR(95%CI), 1.011 (1.007, 1.015); I2 = 77.1%, PAF (95%CI): 1.1 (0.7, 1.5); PM10: RR(95%CI), 1.010 (1.008, 1.013); I2 = 69.1%, PAF (95%CI): 1.1 (0.8, 1.3); PM2.5: RR(95%CI), 1.023 (1.015, 1.031); I2 = 82.8%, PAF (95%CI): 2.3 (1.5, 3.1)]. Sensitivity analyses yielded compatible findings as compared with the overall analyses without publication bias. Stronger associations were found in hospitalized males, children and elderly patients in warm seasons with lag of 2 days or greater. Conclusion Short-term exposures to air pollutants account for increased risks of asthma-related ERVs and hospitalizations that constitute a considerable healthcare utilization and socioeconomic burden.

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

Macrolide therapy in adults and children with non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis.

Background A systematic review and meta-analysis was conducted to evaluate the efficacy and safety of macrolide therapy in adults and children with bronchiectasis. Methods We searched the PUBMED, EMBASE, CENTRAL databases to identify relevant studies. Two reviewers evaluated the studies and extracted data independently. The primary outcome was the number of bronchiectasis exacerbations. Secondary outcomes included exacerbation-related admissions, quality of life (QoL), spirometry, 6-minute walk test (6MWT) and adverse events. Results Nine eligible trials with 559 participants were included. Six were conducted on adults, and the remaining on children. Macrolide therapy significantly reduced the number of patients experiencing one or more exacerbation in adults [risk ratio (RR) = 0.59; 95% CI, 0.40 to 0.86; P = 0.006; I2 = 65%] and children [RR = 0.86; 95% CI, 0.75–0.99; P = 0.04; I2 = 0%], but not the number of patients with admissions for exacerbation. Macrolide therapy was also associated with reduced frequency of exacerbations in adults (RR = 0.42; 95% CI, 0.29 to 0.61; P<0.001; I2 = 64%) and children (RR = 0.50; 95% CI, 0.35 to 0.71; P<0.001). Pooled analyses suggested that spirometry, including FEV1 and FVC, were significantly improved in adults but not in children. Macrolide therapy improved the QoL (WMD, −6.56; 95% CI, −11.99 to −1.12; P = 0.02; I2 = 86%) but no significant difference in 6MWT (WMD, 4.15; 95% CI, −11.83 to 20.13; P = 0.61; I2 = 31%) and the overall adverse events (RR, 0.96; 95% CI, 0.82 to 1.13; P = 0.66; I2 = 0%) in adults. However, reports of diarrhea and abdominal discomforts were higher with macrolide therapy. Conclusions Macrolide maintenance therapy, both in adults and children, was effective and safe in reducing bronchiectasis exacerbations, but not the admissions for exacerbations. In addition, macrolide administration in adults was associated with improvement in QoL and spirometry, but not 6WMT. Future studies are warranted to verify the optimal populations and clarify its potential effects on antimicrobial resistance.

Validation of human small airway measurements using endobronchial optical coherence tomography

BACKGROUND Small airway remodeling is the cardinal feature underlying chronic airway diseases. There is no modality which identifies small airway pathological changes, which is crucial for early diagnosis, efficacy and prognostic assessment. OBJECTIVE To evaluate the usefulness of endobronchial optical coherence tomography (EB-OCT) in assessing small airways morphology in vivo. METHODS Twelve patients with pulmonary nodules scheduled for lung resection underwent spirometry, multi-detector computed tomography (MDCT) and EB-OCT. We measured D(mean) (mean luminal diameter), Ai (inner luminal area), Aw (airway wall area) and Aw% [Aw/(Ai + Aw) × 100%] from the 3rd to 5th generation bronchi of RB9 segment by MDCT. D(mean), Ai, Aw and Aw% from the 3rd to 9th generation bronchi of RB9 segment were measured by EB-OCT and histology. Correlations of these parameters, measured by three different methods, were evaluated. We recruited 4 COPD patients to determine if EB-OCT could identify peripheral airway remodeling. RESULTS The 4 parameters, measured by CT and EB-OCT, correlated significantly [D(mean) (r = 0.991), Ai (r = 0.997), Aw (r = 0.997), Aw% (r = 0.991), all P < 0.01]. Significant correlation were found for these parameters, measured by histology and EB-OCT, from the 3rd to 5th generation bronchi [D(mean) (r = 0.989), Ai (r = 0.997), Aw (r = 0.999), Aw% (r = 0.988), all P < 0.01], and from the 6th to 9th generation bronchi [D(mean) (r = 0.979), Ai (r = 0.997), Aw (r = 0.994) and Aw% (r = 0.988), all P < 0.01]. Significant small airways morphological abnormalities were observed in COPD patients. CONCLUSIONS EB-OCT, a minimally invasive imaging modality with high-resolution, is useful and clinically practical for assessing proximal and distal airways of human compared with CT and histology.

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.

The bronchiectasis severity index and FACED score for bronchiectasis

Bronchiectasis is a chronic airway disease which is associated with cough, sputum production, haemoptysis and/or other distressing symptoms, resulting from various aetiologies [1–4]. The vicious cycle, which consists of airway infection, airway inflammation and structural damage, predominates in the pathogenesis and progression of bronchiectasis [5]. Despite the disappointingly limited number of effective treatment approaches and evidence-based management recommendations, it is imperative to evaluate disease severity meticulously so that better therapeutic outcomes can be achieved. The BSI and FACED scores have complementary roles in the assessment of the severity of bronchiectasis http://ow.ly/Ui7IB