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Community based integrated intervention for preventionand management of chronic obstructive pulmonary disease(COPD) in Guangdong, China: cluster randomised controlledtrial Yumin Zhou, medical doctor,1 Guoping Hu, medical doctor,1 Dali Wang, physician,2 Shaoyi Wang, professor,3Yujun Wang, professor,3 Zhigang Liu, professor,3 Jinxin Hu, medical doctor,1 Zhe Shi, medical doctor,1Gongyong Peng, medical doctor,1 Shengming Liu, professor,1,4 Jiachun Lu, professor,5 Jingping Zheng,professor,1 Jian Wang, professor,1,6 Nanshan Zhong, professor,1 Pixin Ran, professor1 1State Key Laboratory of management of COPD, mainly reflected in the annual rate Respiratory Disease, Guangzhou Objective To evaluate the effects of a community based of decline in FEV1.
Institute of Respiratory Diseases, integrated intervention for early prevention and First Affiliated Hospital, Guangzhou Trial registration Chinese Clinical Trials Registration Medical University, Guangzhou, management of chronic obstructive pulmonary disease (COPD) in China.
2Second Hospital of Liwan District Design Cluster randomised controlled trial.
of Guangzhou, Guangzhou,Guangdong Setting Eight healthcare units in two communities.
Chronic obstructive pulmonary disease (COPD) has 3Bureau of Environmental Participants Of 1062 people aged 40-89, 872 (101 with become a major public health problem worldwide Protection of Liwan District, COPD and 771 without COPD) who fulfilled the inclusion Guangzhou Environmental because of its high and increasing prevalence, morbid- and exclusion criteria were allocated to the intervention or Monitoring Center, Bureau of ity, and mortality.1 2 A recent report estimated that the Environmental Protection of the usual care programmes.
global prevalence of COPD (stage II or over) is about Guangzhou Municipality, Intervention Participants randomly assigned to 10% (12% in men and 9% in women).3 In China, integrated intervention (systematic health education, 4First Affiliated Hospital of Jinan COPD affects 8% of the population aged 40 or intensive and individualised intervention, treatment, and University, Guangzhou, above4 and is one of the top diseases in the World rehabilitation) or usual care.
Health Organization's ranking of burden of diseases.5 Department of Epidemiology, Main outcome measures Annual rate of decline in forced Guangzhou Medical University, It is therefore necessary to develop a reliable inter- expiratory rate in one second (FEV1) before use of Guangzhou, Guangdong vention strategy for prevention and management of Division of Pulmonary and COPD to reduce the burden of this disease.
Critical Care Medicine, Johns Results Annual rate of decline in FEV1 was significantly Hopkins University School of lower in the intervention community than the control Current interventions for COPD (such as smoking Medicine, Baltimore, MD, USA community, with an adjusted difference of 19 ml/year cessation, rehabilitation, nutrition support, drug treat- Correspondence to: P Ran (95% confidence interval 3 to 36) and 0.9% (0.1% to ments, and psychosocial aids) are mainly carried out in pxran@gzhmc.edu.cn and N Zhongnanshan@vip.163.com 1.8%) of predicted values (all P<0.05), as well as a lower hospitals on a case by case basis among patients who annual rate of decline in FEV have already developed moderately or severely symp- 1/FVC (forced vital capacity) Cite this as: BMJ 2010;341:c6387doi:10.1136/bmj.c6387 ratio (adjusted difference 0.6% (0.1% to 1.2%) P=0.029).
tomatic COPD, while little attention has been paid to There were also higher rates of smoking cessation (21% v community based integrated interventions for earlier 8%, P<0.004) and lower cumulative death rates from all stages of the disease or before it has developed.
causes (1% v 3%, P<0.009) in the intervention community Though there has been some progress with case than in the control community during the four year follow- based or hospital based interventions (such as up. Improvements in knowledge of COPD and smoking improvements in exercise capacity, forced expiratory hazards, outdoor air quality, environmental tobacco volume in one second (FEV1), and health related qual- smoke, and working conditions were also achieved (all ity of life, fewer admissions to hospital and acute P<0.05). The difference in cumulative incidence rate of exacerbations, and lower all cause mortality),6-10 the COPD (both around 4%) and cumulative death rate from efficacy of such efforts are limited in the prevention COPD (2% v 11%) did not reach significance between the of COPD among the general population in China.
two communities.
Few patients are diagnosed until they develop severe Conclusions A community based integrated intervention symptoms and signs, and pulmonary function tests are can have a significant impact on the prevention and not routinely performed.4 BMJ ONLINE FIRST bmj.com We carried out a four year community based inte- grated intervention study to establish a reliable strategy All included participants aged 40-89 in these two com- for prevention and management of COPD at its early munities underwent a baseline screening survey to stages or before its development.
evaluate their potential to complete all the acceptablespirometry tests. They then completed questionnaires and gave written informed consent. Exclusion criteria Sampling and randomisation strategy included diagnosis with active tuberculosis, asthma or This community based cluster randomised controlled obvious bronchiectasis, cystic fibrosis, interstitial lung trial ran from September 2002 to May 2007 in Guangz- disease, or pulmonary thromboembolic disease; hou city, China. A multistage randomised sampling malignant tumour; history of thoracotomy with pul- strategy was used. Based on our previous epidemiolo- monary resection; and uncontrolled or serious diseases gical study,4 we used computer generated random and others that could potentially affect the spirometry selection to select one district (Liwang) from 12 dis- test. Participants were lost to follow-up if we could not tricts in Guangzhou city and two communities (Xichun contact them or they had moved to another place, with- and Nanyuan) from nine comparable communities in drew consent, refused to proceed, had invalid data, and the selected district (Liwang). Each was assigned to were unable to complete the study.
intervention or control by simple randomisation (a Integrated intervention coin toss). We then used a computer generated random Three groups in the intervention community list to randomly select five of 15 healthcare units in ("healthy" population, high risk group, and patients Xichun and five of 17 healthcare units in Nanyuan with COPD classified by a baseline investigation) for baseline survey. Two of the 10 healthcare units received the integrated intervention, including sys- were excluded because they did not complete the base- tematic health education and intensive and individua- line survey or refused the follow-up steps. A healthcare lised intervention, treatment, and rehabilitation. To unit is a typical office unit in the community. From all improve outdoor air quality in the intervention com- the people in the units aged 40 and over, we selected munity, residents and the research team made inten- about half (n=1062) using a systematic sampling sive appeals to the local administration for relocation method according to the house number. All sampled and technological upgrading of a neighbourhood subjects were invited to participate in the study by a cement factory. Because of these joint efforts, the phone call or home visits. We allocated 872 people cement factory received technological upgrading tar- who fulfilled the inclusion criteria to integrated inter- geted to reduce air pollution and, in 2005, during the vention or usual care in local communities. They second year and third year of the intervention, relo- underwent follow-up interviews with questionnaires cated to suburban area more than 70 km away.
and spirometry tests in the same hospital at baseline All participants underwent regular systematic health and follow-up survey. We also evaluated improve- education—with health manuals, bulletins, broadcast ments in awareness of health knowledge related to television, video, networks, lectures, free consultation, COPD in random samples drawn from the two com- and holding of relevant knowledge competitions— munities by using the same systematic sampling aimed at improving knowledge about COPD, elimi- method (house number).
nating unhealthy habits and behaviours, and improv-ing indoor and outdoor air quality.
To maximise the effects of the intervention, indivi- Table 1 Baseline characteristics within healthcare units. Figures are numbers (percentages)unless stated otherwise duals with COPD and those at high risk received addi-tional and intensive interventions quarterly in the first Intervention community Control community year and annually in the next three years. These con- sisted of advice and instructions for smoking cessation, Total targeted population aged >40 recommendations for better stoves, kitchen ventila- Mean (SD) population aged >40 per unit tion, work environment and living environment, and Mean (SD) annual income* per unit encouragement on adequate exercises. For smoking cessation we made smokers aware of the adverse effects of smoking on health and the benefits of not <6 years' education smoking, then assessed each smoker's willing to stop smoking and persuaded them to quit. Finally, we made Aware of COPD†‡ personalised plans for each smoker who was willing to Aware of hazards of smoking†: quit smoking. Regular telephone or home visits were performed every three months in the first year and annually thereafter to check smoking status and expo- sure to other risk factors, as well as to encourage com- COPD=chronic obstructive pulmonary disease.
pliance. To prevent relapses, we held advisory and *yuan/person/year; 1 yuan=£0.09, €0.11, $0.15.
recreational activities, lectures, and provided psycho- †Data from random sample of 424 (203 in intervention community, 221 in control community) who completed social support to help and teach smokers how to cope short questionnaire of knowledge on health.
‡Data before intervention were missing for two people.
with withdrawal symptoms such as stress and increases BMJ ONLINE FIRST bmj.com in body weight during smoking cessation. Nicotine Baseline and follow-up survey and outcomes measurement replacement therapy (such as smoking cessation tea All participants filled in questionnaires and underwent and patches) was recommended to relieve cravings spirometry at the baseline and at annual follow-up sur- for tobacco and withdrawal symptoms.
vey. Considerable efforts were made to ensure high qual- In addition, eligible patients with COPD were regu- ity data (see appendix 1 on bmj.com). Our primary larly prescribed a compound bronchodilator (Combi- outcome was the annual rate of decline in FEV1 before vent; salbutamol 120 μg/puff and ipratropium 20 μg/ use of a bronchodilator in the two communities. The sec- puff) for a year and received quarterly visits. Pulmon- ondary outcomes included changes in cumulative inci- ary rehabilitation (such as physical exercise, pursed lip dence rate, cumulative case death rate for COPD, breathing, and abdominal breathing),9 low carbohy- change in awareness of knowledge related to COPD, drate and high protein diets, and other non-pharmaco- and change of risk factors for COPD (such as active and logical treatments were also recommend, and patients passive smoking, outdoor air pollution, living and work- were helped to make plans in terms of training meth- ing environment) from baseline in the two communities.
ods, duration of exercise, and intensity according to guideline. The box summarises the content of the inte- The questionnaires used at baseline and follow-up visits had previously been used in the Burden of ObstructiveLung Disease study in Guangzhou3 and COPD epide- miological survey in China411 (see appendix 2 on Participants in control communities were treated by bmj.com). Additional questionnaires (COPD manage- healthcare providers or general practitioners in the ment and St George's respiratory questionnaire, usual manner. In case of deterioration, participants SGRQ) were used for patients with COPD. We assessed were treated with drugs by following the guidelines and classified changes in risk factors (such as active and from the global initiative for chronic obstructive lung passive smoking, outdoor air pollution, living and work- disease (GOLD) or referral to a respiratory specialist.
ing environment) from baseline as improved, no The content and number of usual care services were change, or worse, based on participants' self report.
not standardised.
From 2002 to 2007 the local bureau of environmentalprotection and environmental monitoring centre con-tinuously measured concentrations of sulphur dioxide(SO2), nitrogen dioxide (NO2), dust deposition, and sul- Components and timings of integrated intervention phation rate with an auto-monitoring system.
All participants (healthy population, those at high risk of COPD, patients with COPD) We classified participants' smoking status at each Systematic health education visit as never smoked, smoking cessation (namely, for- Items or components: mer smoking), and current smoker. Participants whohad smoked for at least six months or had smoked at  Smoking hazards and instruction for smoking cessation least 100 cigarettes in their lifetime were defined as an  Knowledge of COPD and relative risk factors ever smoker,12 13 otherwise they were classed as never Scheme or timings: smoking. Current smokers were those who were smok-  Health manuals, bulletins, etc, in public places quarterly ing tobacco products at the time of the survey and  A lecture and a large scale free consultation twice a year included continual and intermittent smokers and  A competition of knowledge and free spirometry annually those who had quit but restarted or relapsed or hadquit but for less than six months. Smoking cessation Participants at high risk of COPD, patients with COPD (former smoking) was defined as having not smoked Intensive and individualised interventions tobacco products for at least six months at the time of Items or components: survey. We give the rate of smoking cessation during  Advice and instruction for smoking cessation the study period as the ratio of numbers who gave up  Advice to improve air pollution and work environment smoking during the study period to the numbers of  Encouragement to exercise and improvement in living environment current smokers at baseline. Environmental tobacco Scheme or timing: smoke was assessed by asking participants whetherthey could smell tobacco smoke at home or at work  A lecture, a club activity, and a visit quarterly in the first year and annually thereafter for at least an hour a day at each visit.13 We classified Patients with COPD only this by improvement (including no exposure and Treatment and rehabilitation decreased exposure from baseline) or no improvement Items or components: (the same and increased exposure from baseline) based  Treatment with compound bronchodilator for a year on self reports. Exposure to occupational dusts/gases/ fumes for more than a year over a participant Advice and guidance for individualised rehabilitation, drug use, and diet was deemed as having occupational exposure.
 Questionnaire and spirometry quarterly in the first year and annually thereafter  A visit each quarter in the first year for treatment with compound bronchodilator, Trained technicians performed spirometry in accor- advice, and guidance dance with the criteria recommended by the American BMJ ONLINE FIRST bmj.com GlaxoSmithKline) via a 500 ml spacer for those parti- Districts randomly selected from 12 districts in Guangzhou city (n=1, 9 communities) cipants whose FEV1/FVC ratio before bronchodila-tion was <70%. Definition of COPD and its severity Communities randomly selected (n=2, 32 healthcare units) stages were according to the global initiative for chronic obstructive lung disease.16 We used reference Healthcare units randomly selected for baseline survey (n=10, 5 per community) values from the European Coal and Steel Community1993 for predicted values of FEV1, adjusted with con- Healthcare units uncompleted/refused (n=2) version factors for the Chinese population (male 0.95 and female 0.93).17 Healthcare units enrolled to intervention (n=8, 4 per community) Statistical analysis Communities randomised (n=2) To detect the difference of 20 (SD 80) ml in FEV1 between two groups with 80% power, a two sided Community allocated to intervention (n=1) Community allocated to usual care (n=1) type I error of 5%, a design effect of 2.2, and an intra- (4 healthcare units, 523 participants) (4 healthcare units, 539 participants) Received allocated intervention Received allocated intervention cluster correlation coefficient (ICC or ρ, defined as the (4 healthcare units, 436 participants) (4 healthcare units, 436 participants) ratio of the variance between groups to the total var- Did not receive allocated intervention Did not receive allocated usual care iance) of 0.012 based on a pilot study, we calculated (0 healthcare units, 87 participants) (0 healthcare units, 103 participants) Unreachable/died before intervention Unreachable/died before intervention that we needed eight clusters of 130 participants according to usual formula,18 allowing 20% loss during Refused (n=27, 5%) Refused (n=46, 9%) Invalid data at baseline survey (n=30, 6%) Invalid data at baseline survey (n=24, 5%) follow-up. The statistical analysis was performed withthe SAS version 9.1 software (SAS Institute, Cary, Completed follow-up: Completed follow-up: 1 year: 417 participants 1 year: 428 participants We included in the analyses all recruited participants 2 year: 409 participants 2 year: 415 participants who had received the allocated intervention or usual 3 year: 401 participants 3 year: 414 participants 4 year: 409 participants 4 year: 410 participants care, except those without any acceptable observation Uncompleted follow-up participants: Uncompleted follow-up participants: data after randomisation. Baseline characteristics were 1 year: 16 missing; 3 withdrew consent; 0 died 1 year: 6 missing; 2 withdrew consent; 0 died t test or analysis of variance for con- 2 year: 22 missing; 4 withdrew consent; 1 died 2 year: 15 missing; 3 withdrew consent; 3 died tinuous variables and a χ2 test for dichotomous vari- ables. Improvements in awareness and risk factors for 3 year: 25 missing; 6 withdrew consent; 4 died 3 year: 10 missing; 3 withdrew consent; 9 died COPD between the two communities were analysed 4 year: 15 missing; 6 withdrew consent; 6 died 4 year: 8 missing; 3 withdrew consent; 15 died with hierarchical logistic models, taking account of the clustering nature of the data. The latest valid values with respect to change of awareness and risk factors for Analysis (4 healthcare units): Analysis (4 healthcare units): COPD were regarded as the endpoint values for those Questionnaires (n=436) Questionnaires (n=436) Spirometry (n=429) Spirometry (n=431) who did not complete follow-up.
Excluded from spirometry analysis Excluded from spirometry analysis Preliminary data analysis showed that the pattern of 7 with invalid data 5 with invalid data change in absolute values of FEV1 (ml), percentage ofpredicted value, and FEV1/FVC ratio (%) from base- Fig 1 Flow of participants through trial. Missing indicates participants with missing data line was about linear and varied according to baseline because of failure of contact, being out, or inability to finish spirometry test; they might attend data. To access longitudinal changes of FEV1 (often next follow-up visits. Withdrew indicates cumulative number of participants who withdrew called FEV1 ‘‘slope'') between the intervention and consent (refusal); they were invited to complete investigation with questionnaire before control community, we applied SAS procedure, which admits missed values, to build multi-level mixed models by adjusting for confounding and Thoracic Society14 and the Europe Respiratory clustering effects. Potential confounders were taken Society.15 At least three acceptable and two reproduci- into account, and we included baseline FEV1 (or ble measurements (that is, largest and next largest FEV1/FVC ratio), age, sex, education, smoking status, values of forced vital capacity (FVC) and FEV1 within environmental tobacco smoke, COPD, body mass 150 ml or 5%) that met with the criteria14 15 were index (BMI), and occupational exposure to dusty/ required for each individual. The largest value of gases/fumes in the final model. The selection of the FVC and FEV1 was reported (see appendix 1 on appropriate type of covariance structure was accom- bmj.com). To minimise the variation of the results, on plished by considering the biological features of the each of the four testing days during the four year study outcome variable and also by choosing the smallest (one day a year) spirometry was performed for each Akaike's information criterion (AIC) after fitting mod- participant at about the same time of day. The use of els with alternative covariance structures. The final short and long acting bronchodilators was prohibited models included an auto regressive order 1 structure within 12 or 24 hours before the test, respectively. A covariance (AR(1)) to count for serial correlation of portable spirometer (Micro Medical, Chatham, Kent) FEV1 and FEV1/FVC within individuals and an was used and the test was done after inhalation of 400 unstructured covariance to account for random varia- μg of salbutamol for 15-20 minutes (Ventolin, tion in the intercept and slope parameters between BMJ ONLINE FIRST bmj.com Table 2 Baseline characteristics of participants randomly selected from two communities.
and sulphation rate. The correlation of adjusted FEV1 Figures are numbers (percentages) unless stated otherwise at each year with average level of air pollutants frombaseline was analysed with partial correlations analy- Intervention community Control community sis. Significance was set at P<0.05.
No of participants Baseline characteristics and follow-up rate Of 1062 sampled participants, 872 (82%) who fulfilled the criteria of study were allocated intervention or usual care. Of these, 845 (80%) completed follow-up Years of education: at the first year, 824 (78%) at the second year, 815 (77%) at the third year, and 819 (77%) at the fourth year. A total of 872 (82%) completed the baseline sur- vey and at least one follow-up investigation with ques- tionnaires (83% in the intervention community and 81% in the control community), and 860 (80%) had acceptable data for spirometry test from at least two follow-up visits (including baseline) (82% in the inter- Mean (SD) FEV1 (l) vention community and 80% in the control commu- Mean (SD) % predicted FEV1 nity) (fig 1). There were 840, 822, and 793 Mean (SD) FVC (l) participants who completed an acceptable spirometry Mean (SD) % predicted FVC test for three, four, and five years (including baseline), Distribution of COPD and non-COPD There was no difference in causes of allocation fail- Healthy population ure between the two communities (P=0.11, fig 1) andno difference in the main basic demographic character- High risk for COPD istics (see table A in appendix 3 on bmj.com). There was a significant difference in causes of uncompleted follow-up (dropping out) for spirometry tests between Stage III COPD or over the communities at the end of study (P=0.03, fig 1). The Reversibility among COPD‡ two communities were drawn from a single district and Previous diagnosis of respiratory disorders were similar in socioeconomic status (that is, annual Respiratory symptoms averaged income and education level), availability of Occupational history of dusts/gases/fumes§ and access to health services, current smoking preva- Respiratory infection during childhood lence, awareness of COPD, and main demography at Smoking status at baseline survey: baseline (table 1). At baseline the intervention commu- nity had a higher concentration of SO2 and sulphation Smoking cessation rate in outdoor air than the control community (P<0.001 and P=0.018, respectively), but there was Smoking amounts (pack years) no difference at the end of study (fig 2). Compared Exposed to environmental tobacco smoke¶ with the control community, the intervention commu- BMI=body mass index; FEV1=forced expiratory volume in one second; FVC=forced vital capacity; COPD=chronic nity had a greater rate of decline in SO2 concentration obstructive pulmonary disease.
*Lower in participants without COPD in intervention community than in control community (80.71 (7.95) µg/m3 per year (95% confidence interval 0.019 (6.76), P=0.001).
to 0.083) P=0.003) and dust deposition (0.051 (0.019 to †Post-bronchodilator data used in participants with COPD; bronchodilation not carried out those without COPD.
0.083) kg/km2/month per year, P=0.003) during fol- ‡Reversibility of COPD defined as improvement in FEV1 from pre-bronchodilator ≥12% and ≥200 ml post-bronchodilator.
low-up, and there was a difference of borderline signif- §Two communities had similar characteristics at baseline except for occupational history of dust/gases/fumes icance between the two communities in the slope of concentration of NO ¶Data missing for 12 participants (seven in intervention community and five in control community).
2 (0.033 (−0.013 to 0.079) µg/m3 per year, P=0.092) and sulphation rate (0.020 (−0.001to 0.041) µg SO3/100 cm2 PbO2/day/year, P=0.059).
individuals and healthcare units. Such an analysis was Most baseline demographic characteristics of parti- repeated in subgroups.
cipants who completed questionnaires during follow- We used a mixed model to compare the change in air up were comparable between the two communities, pollutants (log transformed) in the two communities.
except for occupational dusts/gases/fumes exposure As preliminary analysis showed significant or close to (P<0.001) (table 2). Similar results were observed significant correlations between pairs of pollutants among those 860 people who had completed accepta- (data not shown), they can be regarded as a correlated ble spirometry tests (data not shown).
"package" of pollutants with a similar pattern relativeto each other across the four year study period. We FEV1 and FEV1/FVC ratio extracted a variable to represent these air pollutants During follow-up, the mean rate of decline in FEV1 using factor analysis for SO2, NO2, dust deposition, was about 19 ml and 0.9% of the predicted value per BMJ ONLINE FIRST bmj.com Table 3 Difference between two communities in annual rate of decline in FEV than those without any improvement, after adjustment predicted %/year) and FEV1/FVC ratio (%/year) in participants aged ≥40 for confounders and clustering effects (table D inappendix 3 on bmj.com). Non-smokers in the inter- Adjusted difference* vention community still had a slower rate of declineof FEV 1 than those in the control community by 23 ml (12 to 33) per year and 1.2% (0.7% to 1.8%) of predicted value per year) (table D in appendix 3 on bmj.com). Differences between the two communities FEV1 (predicted %/year) in current smokers were smaller (data not shown).
FEV1/FVC (%/year) Participants without COPD Changes in awareness of and risk factors for COPD By the end of the study, awareness of COPD in the FEV1 (predicted %/year) intervention community improved from 20% to 77% FEV1/FVC (%/year) compared with 18% to 22% in the control community *Adjusted for baseline FEV1 (or FEV1/FVC), age, sex, education, smoking status, COPD, BMI (body mass index), (P<0.001). Similarly, more people reported awareness and occupational exposure to dusty/gases/fumes) and clustering effects.
of the risks or hazards of cigarette smoking, despite nosignificant difference for awareness of COPD and year higher in the control community than in the inter- related risk factors at baseline (table 1 and table 4).
vention community (49 ml/year v 30 ml/year; 1.2% v Compared with the control community, more peo- 0.3% of predicted values per year). The FEV1/FVC ple in the intervention community reported an ratio declined in the control community but not in improvement in outdoor air pollution (27% v 19%), the intervention community (0.4% v −0.5% a year).
working conditions (6% v 3%), and environmental After adjustment for confounders and clustering tobacco smoke (61% v 52%) (table 4). The rate of smok- effects, statistical effects persisted for intervention com- ing cessation in intervention community was 21%, munity in the rate of decline (P<0.05, table 3 and fig 3).
which is higher than that in the control community At the end of the study the intervention community (8%) (table 4). Although there were no significant dif- had a significantly greater estimated mean FEV1 and ferences between the two communities in cumulative FEV1/FVC ratio than the control community (P<0.05, incidence of COPD (both around 4%) and cumulative fig 3). In the total population, the differences were death rate of COPD (2% v 11%), there were differences 71 ml (95% confidence interval 47 to 94) for FEV1, in cumulative death rate from all causes in the total 3.0% (1.7% to 4.2%) for predicted value, and 3.1% population during follow-up (1% v 3%, P=0.009) (2.4% to 3.9%) for FEV1/FVC ratio. Similar results (table 4). We found no overall difference with regard were observed among participants without COPD, to quality of life (scores of St George's respiratory ques- with figures of 85 ml (61 to 110, 4.3% (3.0% to 5.6%), tionnaire) among patients with COPD between two and 3.0% (2.3% to 3.8%), respectively (fig 3).
communities. Patients with COPD who had received Further subgroup analyses showed similar results in integrated intervention for a year, however, showed the rate of decline of FEV1 and the change of FEV1/ improved quality of life as indicated in symptom scores FVC ratio with regard to the effects of intervention on the respiratory questionnaire and experienced less among people without COPD (table 3 and fig 3).
exacerbation of COPD compared with those in the Results were also similar in participants at high risk control community (data not shown).
(see table B in appendix 3 on bmj.com). There was nosignificant difference between patients with COPD Changes of outdoor air quality from the two communities in the rate of decline of As shown in figure 2, there was a greater decline in SO2 FEV1 within four years or in FEV1/FVC ratio (table concentration (0.051 (0.019 to 0.083) µg/m3 per year, B in appendix 3 on bmj.com).
P<0.003) and dust deposition (0.051 (0.019 to 0.083) As shown in the subgroup analysis of smoking, in kg/km2/month per year, P<0.003) in the intervention intervention communities the decline in FEV1 values community than in the control community. There (both absolute value (ml) and percentage of predicted were borderline differences between the two commu- value (% predicted)) was slower in those who had never nities in the slope of concentration of NO2 (0.033 smoked or had quit smoking than in current smokers (−0.013 to 0.079) µg/m3 per year, P>0.09) and sulpha- after adjustment for confounders and clustering effects tion rate (0.020 (−0.001 to 0.041) µg SO3/100 cm2 (P<0.05, table C in appendix 3 on bmj.com). A similar PbO2/day/year, P>0.05). These results indicate that pattern but with no difference in decline of FEV1 was outdoor air quality was significantly improved in inter- founded among subgroups by smoking status in the vention community compared with the control com- control community (table C in appendix 3 on Further analysis of non-smokers (including never smokers and former smokers) showed that non-smo- Principal findings and comparison kers with reported improvement in exposure to envir- Community based integrated intervention at earlier onmental tobacco smoke seemed to have a slower rate stages of COPD and before its development could sig- of decline of FEV1 by 0.6% of predicted value per year nificantly slow the decline in FEV1. To our knowledge, BMJ ONLINE FIRST bmj.com Cement factory relocated Cement factory relocated Fig 2 Annual log mean levels of air pollutants in intervention and control communities, 2002-2007, with 95% confidenceintervals few studies have directly elucidated the effects of inte- FEV1 (by −27 ml/year) in the intervention community grated intervention on COPD at the community level.
(table C in appendix 3 on bmj.com). In the control The multiple risk factor intervention trial (MRFIT),19 community, there was no significant difference in which focused on coronary heart disease, found no annual rate of decline in FEV1 between those who overall differences in the rate of decline in FEV1 did and did not stop smoking, which could be between two communities (usual care and special inter- explained by the low numbers of participants who vention that included an intensive smoking cessation had quit smoking and the fact that some of them gave programme), but FEV1 declined slowly among smo- up smoking because of worsening health status. There- kers who did not take β blockers in the tobacco cessa- fore, there seems little question that smoking cessation tion intervention group compared with controls. In greatly contributed to the outcome of the intervention.
Lung Health Study,20 aggressive smoking interventions Other factors besides smoking cessation should also were given to smokers with mild COPD, and this strengthen the positive benefits of intervention. We resulted in a slower decline in FEV1 in the first year found a significant difference in the rate of decline in between the two groups, but there were no differences FEV1 between the two communities after adjustment in the next three years. In contrast, our community for smoking cessation, as well as in non-smokers (table based interventions targeted more aspects of COPD D in appendix 3 on bmj.com). As shown in our results, management and prevention at its earlier stages or more people reported having improved exposure to before development. As a result, we saw a slower rate environmental tobacco smoke from baseline in the of decline in FEV1 among participants in the inter- intervention community than in control community vention community than in the control community.
during follow-up. Those who reported having reduced Meanwhile, there was an improvement in FEV1/FVC exposure to environmental tobacco smoke at the end ratio among participants in intervention community, of study had a slower rate of decline in FEV1 than those especially among those at high risk of COPD.
without reduced exposure (table D in appendix 3 on The benefits of our integrated intervention could bmj.com). These observations indicated that changes have resulted from a combination of smoking cessa- in exposure to environmental tobacco smoke might tion, efforts to improve environmental air quality, self have contributed to the effects of intervention.
management training for prevention of COPD, andother positive factors.
Air pollutionAs an important part of the community based inter- vention programme and after joint efforts of members Smoking accelerates the decline in FEV1, but it can be of the study team, public, and government, a neigh- reversed by quitting smoking.6 19-23 In our study there bourhood cement factory near the intervention com- was a greater cessation rate in the intervention commu- munity was eventually relocated and upgraded in 2005 nity than in the control community (21% v 8%). Cessa- with the main purpose of decreasing air pollution. This tion was associated with a reduced rate of decline in resulting improvement in outdoor air pollution was BMJ ONLINE FIRST bmj.com No of participants Fig 3 Estimated mean FEV1 (ml and % predicted) and FEV1/FVC ratio (%) over time in both communities among totalpopulation and those without COPD. *P<0.05 for estimated mean after adjustment for clustering and confounding factors(baseline FEV1 (or FEV1/FVC ratio), age, sex, education, smoking status, environmental tobacco smoke, COPD, BMI, andoccupational exposure to dust/gases/fumes). P values in figure refer to comparison between communities in rate of decline inFEV1 and FEV1/FVC ratio after adjustment for above confounders and clustering effects noted in laboratory reports from a perennial monitor- Education and knowledge ing site in the intervention community designated by Though health education did not seem to have obvious the local bureau of environmental protection (fig 2). In and directly positive effects on the rate of decline in contrast, data from the monitoring site in the control FEV1 (data not shown), previous trials have shown community showed no improvement in air quality.
that it can help to reduce exacerbation of and mortality After adjustment for potential confounders and cluster from COPD and improve quality of life.9 25 26 As lower effects, there were still significant differences in the sur- respiratory disorders or acute exacerbations of COPD rogates for the change in outdoor air quality between also promote decline in FEV1 in current smokers with the two communities, and similar results were mild COPD,27 reduction in acute exacerbations should observed among those who had never smoked (table also have a positive effect on decline of FEV1. Further- D in appendix 3 on bmj.com). In addition, there was more, as COPD is considered a disease in which limita- significant correlation between adjusted FEV1 and tion of air flow associated with harmful gases and fumes FEV1/FVC ratio and averaged air pollutants over is not fully reversible, education targeted at avoidance time (table E in appendix 3 on bmj.com). Therefore, of risk factors might have played an important role in improvement in air pollution within the intervention reducing the decline of FEV1. At baseline 78% of the community should also have contributed to the slower participants knew little about COPD and over 65% had decline in FEV1, which is consistent with previous pub- never received health education. This poor level of lished literature. 24 COPD prevention among people at baseline could BMJ ONLINE FIRST bmj.com Table 4 Awareness of health knowledge, change of risk factors, cumulative incidence rate, rehabilitation, nutrition support, drug treatment, and and case death rate between two communities after intervention health education),6-919 20 should be more effectiveregarding development and progression of the disease Control community Adjusted odds ratio than a single intervention targeted at a sole factor.
COPD has a long term course with chronic progres- Awareness of COPD†: sion and is often underdiagnosed, and thus a commu- nity based integrated intervention at earlier stages or 12.13 (8.46 to 17.39) before development of COPD would have more Awareness of smoking hazard†: impact than a hospital intervention among patients who have already developed moderately or severely 2.11 (1.25 to 3.56) symptomatic COPD. Our hypothesis is consistent 2.68 (1.61 to 4.44) with the results of several recent studies.28-30 These stu- Outdoor air pollution‡: dies have shown that FEV1 declined more rapidly in 1.42 (1.02 to 1.98) patients with milder COPD, indicating that more attention should be paid to patients with earlier stage 0.74 (0.53 to 1.05) disease. Our results further emphasise the importance Working conditions: of intervention before the development of COPD.
1.73 (0.88 to 3.39) Our study had certain limitations. Firstly, fewer par- ticipants in the intervention community had occupa- 0.42 (0.15 to 1.20) tional exposure to dust/gases/fumes at baseline. We Environmental exposure to tobacco smoke§: consider that this imbalance did not compromise our 1.48 (1.32 to 1.68) conclusion because we found a significantly slower rate of decline in FEV1 in the intervention community even Smoking status at end of study: after adjustment for these factors. This was also the case in further analyses stratified by occupational exposure 0.72 (0.52 to 0.99) to dust/gases/fumes (fig A in appendix 4 on bmj.com).
1.36 (0.95 to 1.93) Secondly, changes in risk factors such as smoking sta- Stopped smoking during study period: tus were not based on laboratory measurement but on self report. This did not change our conclusions as we 3.10 (1.44 to 6.67) also obtained information from close family members Cumulative incidence of COPD** of the participants. Our results also showed that smok- 0.98 (0.49 to 2.00) ing cessation slowed the rate of decline in FEV1 (table B in appendix 3 on bmj.com), confirming results of other studies.6 19-21 In addition, despite there being a Cumulative deaths from COPD correlation between adjusted FEV 0.17 (0.02 to 1.50) 1 and air pollutants over time (table E in appendix 3 on bmj.com), we could not further confirm the correlation of annual rate of Cumulative deaths from all causes decline in FEV1 and change of outdoor air quality 0.23 (0.08 to 0.69) because we recruited only two communities. Finally, we evaluated the annual decline of FEV1 only before *Adjusted for clustering effects. Odds ratio >1 means that over four years more people in interventioncommunity than control community reported improvement in variables. After adjustment for clustering effect, use of a bronchodilator, not after, because a broncho- when variables were considered as ordered categories and cumulative logit model was used, odd ratios were dilator test was not performed among patients without 1.66 (1.24 to 2.22, P<0.001) for awareness of hazards of smoking, 1.52 (1.17 to 1.97, P<0.002) for outdoor air COPD at baseline. COPD was defined by a FEV1/ pollution, and 1.94 (1.09 to 3.44, P=0.024) for working conditions.
†After intervention 341 in intervention community and 331 in control community randomly sampled from entire FVC ratio of below 0.7 after use of bronchodilator.
population completed short questionnaire of knowledge on health.
This criterion, however, could result in overdiagnosis ‡Data missing for four in intervention community and one in control community.
§Data missing for seven in intervention community and five in control community.
in older people and underdiagnosis in younger ¶Four former smokers at baseline (two in each community) had started smoking at end of study.
people.31 Diagnosis by percentage of FEV1/FVC **Diagnosis of COPD was according to global obstructive lung disease in 12 participants. Excludes participants ratio below the fifth centile should be more precise.32 who did not undergo post-bronchodilator test and those with pre-bronchodilator FEV1/FVC ≥70%.
Unfortunately, the lower limit of normal for FEV1/FVC ratio for people in China is not currently avail- also explain the greater outcomes achieved by this well able. In addition, a fixed ratio of FEV1/FVC below 0.7 designed health education programme in our inte- is still recommended by the global initiative for chronic obstructive lung disease (GOLD) and is used by manyother investigators.3 33 We therefore used the fixed Strengths and limitation of the study ratio of 0.7 for diagnosis of COPD in our study.
Our integrated community based interventionachieved positive effects, especially for people at high Conclusion and implications risk of COPD. As COPD is a disease that can be caused In conclusion, this community based integrated inter- by multiple factors, an integrated intervention, which vention helped to prevent and control COPD through was formed and refined from published methods (such improved awareness of COPD, reduced risk factors for as smoking cessation, reduce of air pollution, COPD, and a reduction of the rate of decline in FEV1.
BMJ ONLINE FIRST bmj.com Chan-Yeung M, Aït-Khaled N, White N, Ip MS, Tan WC. The burden WHAT IS ALREADY KNOWN ON THIS TOPIC and impact of COPD in Asia and Africa. Int J Tuberc Lung Dis2004;8:2-14.
COPD is a chronic progressive disease caused by multiple factors such as smoking and air Scanlon PD, Connett JE, Waller LA, Altose MD, Bailey WC, Buist AS.
pollution; a single factor intervention will therefore have limited effects Smoking cessation and lung function in mild-to-moderate chronicobstructive pulmonary disease. The Lung Health Study. Am J Respir Little attention has been paid to interventions at an earlier stage at community based level Crit Care Med 2000;161:381-90.
Tabak C, Smit HA. Diet and chronic obstructive pulmonary disease:independent beneficial effects of fruits, whole grains, and alcohol WHAT THIS STUDY ADDS (the MORGEN study) Clin Exp Allergy 2001;31:747-55.
Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, et al. A Community based integrated interventions can decrease the rate of decline in FEV1, probably 4-year trial of tiotropium in chronic obstructive pulmonary disease. N from the combined effects of smoking cessation and improvements in air pollution Engl J Med 2008;359:1543-54.
Troosters T, Casaburi R, Gosselink R, Decramer M. Pulmonaryrehabilitation in chronic obstructive pulmonary disease. Am J Respir Though the methods used in this integrated inter- Crit Care Med 2005;172:19-38.
10 Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, vention and our experience with it might be culture et al. Salmeterol and fluticasone propionate and survival in chronic and condition specific, the outcomes that smoking ces- obstructive pulmonary disease. N Engl J Med 2007;356:775-89.
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environmental tobacco smoke have contributed to the 12 Gu D, Wu X, Reynolds K, Duan X, Xin X, Reynolds RF, et al. Cigarette slowing rate of decline in FEV smoking and exposure to environmental tobacco smoke in China: 1 should apply through- the international collaborative study of cardiovascular disease in out the world.
Asia. Am J Public Health 2004;94:1972-6.
13 Yang G, Fan L, Tan J, Qi G, Zhang Y, Samet JM, et al. Smoking in China, We thank Xiaoyi Yang (National Cancer Institute, NIH, USA) and finding of the 1996 national prevalence of survey. JAMA Guangqiao Zeng (State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, Guangzhou Medical 14 American Thoracic Society. Standardization of spirometry. 1994 University, China) for their help with English, and Mei Jiang (State Key update. Am J Respir Crit Care Med 1995;152:1107-36.
Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory 15 Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, Diseases, Guangzhou Medical University, China) for her help with the et al. Interpretative strategies for lung function tests. Eur Respir J statistical analysis. We also thank Jinquan Liang, Tianming Dong, and Yexin Liu (Bureau of Environmental Protection of Liwan District, 16 Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, et al.
Global strategy for the diagnosis, management, and prevention of Guangzhou Environmental Monitoring Center, Bureau of Environmental chronic obstructive pulmonary disease: GOLD executive summary.
Protection of Guangzhou Municipality) for their help in measuring air Am J Respir Crit Care Med 2007;176:532-55 17 Zheng J, Zhong N. Normative values for pulmonary function testing in Contributors: YZ collected the data and monitored data collection, Chinese adults. Chin Med J (Engl) 2002;115:50-4.
planned the statistical analysis, analysed the data, and drafted and 18 Donner A, Klar N. Design and analysis of cluster randomization trials revised the manuscript. GH and DW implemented the trial and conducted in health research. Oxford University Press, 2000.
the intervention. SW, YW, and ZL conducted and monitored data 19 Browner WS, DuChene AG, Hulley SB. Effects of the Multiple Risk collection. JH and ZS conducted intervention. GP and SL conducted data Factor Intervention Trial smoking cessation program on pulmonary collection. JL planned the statistical analysis and drafted and revised the function—a randomized controlled trial. West J Med 1992;157:534-8 20 Anthonisen NR, Connett JE. Effects of smoking intervention and the paper. JZ monitored data collection and drafted and revised the paper. JW use of an inhaled anticholinergic bronchodilator on the rate of drafted and revised the paper. PR and NZ initiated and designed the decline of FEV1 the lung health study. JAMA 1994;272:1497-505.
project, monitored data, and drafted and revised the paper. PR, NZ, and 21 Willemse BW, Postma DS, Timens W, ten Hacken NH. The impact of YZ are guarantors.
smoking cessation on respiratory symptoms, lung function, airway Funding: This study was funded by a grant from the Chinese Central hyperresponsiveness and inflammation. Eur Respir J Government key research projects of the 10th National Five-year Development Plan 2001BA703B03(A) and in part by Guangdong Key 22 Omori H, Nonami Y, Morimoto Y. Effect of smoking on FEV1 decline in Research Project grant B30301. The researchers were independent from a cross-sectional and longitudinal study of a large cohort of Japanesemales.
funders. The study funders had no influence on the study design, 23 Tager I, Segal MR, Speizer FE, Weiss ST. The natural history of forced collection, analysis, interpretation of data, writing of the report, and the expiratory volumes—Effect of cigarette smoking and respiratory decision to submit the article for publication.
symptoms. Am Rev Respir Dis 1988;138:837-49.
Competing interests: All authors have completed the Unified Competing 24 Gauderman WJ, Avol E, Gilliland F, Vora H, Thomas D, Berhane K, Interest form at www.icmje.org/coi_disclosure.pdf (available on request et al. The effect of air pollution on lung development from 10 to from the corresponding author) and declare: no support from any 18 years of age. N Engl J Med 2004;351:1057-67. [Erratum in N Engl J institution for the submitted work; no financial relationships with any Med 2005;352:1276.] institutions that might have an interest in the submitted work in the 25 Garcia-Aymerich J, Hernandez C, Alonso A, Casas A, previous 3 years; no other relationships or activities that could appear to Rodriguez-Roisin R, Anto JM, et al. Effects of an integrated careintervention on risk factors of COPD readmission. Respir Med have influenced the submitted work.
Ethical approval: The study protocol was approved by medical ethic 26 Casas A, Troosters T, Garcia-Aymerich J, Roca J, Hernadez C, Alonso A, committee of Guangzhou Institute of Respiratory Diseases and written et al. Integrated care prevents hospitalisations for exacerbations in informed consent was given by all participants.
COPD patients. Eur Respir J 2006;28:123-30.
Data sharing: No additional data available.
27 Kanner RE, Anthonisen, Connet JE. Lower respiratory illnesses promote FEV1 decline in current smokers, but not ex-smokers withmild chronic obstructive pulmonary disease: results from the Lung Sin DD, Stafinski The impact of chronic obstructive pulmonary Health Study. Am J Respir Crit Care Med 2001;164:358-64.
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Buist AS, McBurnie MA, Vollmer WM, Gillespie S, Burney P, 29 Celli B, Thomas N, Anderson J, Ferguson JT, Jenkins CR, Jones PW, Mannino DM, et al. International variation in the prevalence of COPD et al. Effect of pharmacotherapy on rate of decline of lung function in (the burden of obstructive lung disease study): a population-based chronic obstructive pulmonary disease. Am J Respir Crit Care Med prevalence study. Lancet 2007;370:741-50.
Zhong N, Wang C, Yao W, Chen P, Kang J, Huang S, et al. Prevalence of 30 Bridevaux PO, Gerbase MW, Probst-Hensch NM, Schindler C, chronic obstructive pulmonary disease in China—a large population- Gaspoz JM, Rochat T. Long-term decline in lung function, utilisation based spirometry based cross-sectional survey. Am J Respir Crit Care of care and quality of life in modified GOLD stage 1 COPD. Thorax BMJ ONLINE FIRST bmj.com 31 Hansen JE, Sun XG, Wasserman K. Spirometric criteria for airway 33 Menezes AM, Perez-Padilla R, Jardim JR, Muino A, Lopez MV, obstruction: Use percentage of FEV1/FVC ratio below the fifth Valdivia G, et al. Chronic obstructive pulmonary disease in five Latin percentile, not <70%. Chest 2007;131:349-55.
American cities (the PLATINO study): a prevalence study. Lancet 32 Swanney MP, Ruppel G, Enright PL, Pedersen OF, Crapo RO, Miler JR, et al. Using the lower limit of normal for the FEV1/FVC ratio reducesthe misclassification of airway obstruction. Thorax 2008;63:1046-51 Accepted: 18 September 2010 BMJ ONLINE FIRST bmj.com

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