Early Detection and Impaired Quality of Life in COPD GOLD Stage 0: A Pilot Study

Abstract

This pilot study aimed to identify early stages of chronic obstructive pulmonary disease (COPD) in an urban population of smokers and ex-smokers using the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2001, 2003) classification guidelines and to assess the impact of early disease on quality of life. Smokers and ex-smokers of ≥ 10 pack years and age ≥ 50 years were recruited. After an initial telephone interview, eligible subjects completed a clinical assessment, spirometry tests, and the St. George's Respiratory Questionnaire (SGRQ). A total of 244 subjects completed the study; 91 subjects (37%) were normal, 153 subjects (63%) met the criteria for GOLD stages 0 to III: 65 stage 0 (27%), 43 stage I (18%), 38 stage II (16%), 7 stage III (3%) and 0 in stage IV. The stage 0 patients were younger than any other COPD groups (p < 0.0005), including normal subjects (55.5 ± 5.4 years vs. 59.6 ± 7.2 years; p = 0.0005). The frequency of current smoking in stage 0 patients was greater than those in the normal category (80% vs. 33%; p < 0.0001). There were significant impairments in quality of life measures between normal subjects and all GOLD stages (SGRQ total scores; p < 0.0001) except for stage I (SGRQ total scores; p = 0.1409). Subjects with COPD at GOLD stage 0 were markedly under-diagnosed. These subjects had a significant impairment in their health-related quality of life measures, were younger than other categories, and were mostly current smokers. Thus, detection of COPD at GOLD stage 0 may provide a unique opportunity for early intervention and smoking cessation and the removal of GOLD stage 0 from the 2006 update should be re-assessed.

Key words: :

• COPD
• Stage 0
• GOLD classification guidelines
• Smokers
• Quality of life
• FEV1

Abbreviations
ATS:	=	American Thoracic Society;
BMI:	=	Body Mass Index;
COPD:	=	Chronic Obstructive Pulmonary Disease;
FEV1:	=	Forced Expiratory Volume in 1 second;
FEV6:	=	Forced Expiratory Volume in the first 6 seconds;
FVC:	=	Forced Vital Capacity;
FVC6:	=	Forced Vital Capacity in the first 6 seconds;
GOLD:	=	Global Initiative for Chronic Obstructive Lung Disease;
ICS:	=	Inhaled Corticosteroids;
LABA:	=	Long acting beta 2 agonist;
PPY:	=	Pack years;
SABA:	=	Short acting beta 2 agonist;
SD:	=	Standard Deviation;
SGRQ:	=	St. George's Respiratory Questionnaire;
TSQ,	=	Telephone Screen Questionnaire

INTRODUCTION

Chronic obstructive pulmonary disease (COPD) is a respiratory disorder largely caused by smoking. It is characterized by progressive, partially reversible airway obstruction and lung hyperinflation, systemic manifestations, and increasing frequency and severity of exacerbations ([1]). In Canada, COPD is the fourth leading cause of death in both men and women ([2]). By the year 2020, it is predicted that COPD will be the third most common cause of death worldwide ([3]). Despite the increase in public awareness of the hazards of smoking and a possible decrease in the number of people smoking cigarettes, the frequency of COPD and associated mortality rates continue to rise ([2]). Although estimates of COPD frequency vary with populations studied and spirometry criteria used, there is evidence that it is underestimated, mainly in the early stages ([4], [5], [6]). The Global Initiative for Chronic Obstructive Lung Disease (GOLD 2001) guidelines highlight the importance of a global strategy for the diagnosis, management and prevention of COPD ([7], [8]). GOLD 2001 had a five-stage COPD severity classification to guide physicians in their therapeutic approach to the disease ([7], [8]). GOLD was updated in late 2006 ([9]) with the removal of stage 0 (subjects with symptoms but normal lung function), the relevance of which was challenged upon reviewing the results of the current pilot study.

COPD is an insidious and slowly progressive disorder that is often associated with a significant pulmonary impairment at the time of initial clinical presentation. This may be related to under-utilization of case-finding strategies such as screening for chronic respiratory symptoms and spirometry in at-risk populations. The GOLD guidelines underscore the importance of chronic cough and sputum production prior to airflow obstruction to identify subjects at risk for COPD. To date, it is unclear whether GOLD stage 0 subjects with chronic respiratory symptoms and normal lung function experience a substantial impairment in quality of life compared with normal individuals. The purpose of this pilot study was to identify patients with early stages of COPD in an urban population of commuter smokers and ex-smokers based on the GOLD 2001, 2003 classification guidelines, and to assess the impact of early stages of COPD on quality of life as measured by the St. George's Respiratory Questionnaire (SGRQ). The results from this pilot study may provide the rationale for a larger-scale study.

MATERIALS AND METHODS

Patients

Male and female subjects were recruited with the aid of newspaper advertisements, which read as follows: “Volunteers are wanted for a research study investigating the effects of smoking on lungs and breathing. Interested candidates must be: 1. 50 years of age or older and 2. A cigarette smoker of at least 10 years or an ex-cigarette smoker of at least 10 years. If you fit these criteria, you may be eligible to participate. To be evaluated please contact our clinic”. To minimize any potential for investigator-selection bias, the paper advertisements asked only for the volunteer's age and smoking history without the requirement of having any symptoms. In order to reduce the risk of recruiting patients with asthma, the study targeted subjects with a significant history of smoking and advanced age. Further, a history of asthma was an exclusion criterion. There were no questions asked regarding respiratory symptoms in either the newspaper advertisements or the Telephone Screen Questionnaire (TSQ). These commuter newspapers were distributed during the morning rush hour, primarily through transit systems and street boxes located across the Greater Toronto area. Readership is almost equally distributed between sexes (48% and 52%, males and females, respectively) and 27% of readers are aged ≥ 50 years ([10]).

Study design

This was an observational, single-site study consisting of telephone screening followed by a single study visit from December 2000 to July 2001. Responders called the clinic and, after giving verbal informed consent, were assessed for eligibility by the TSQ to verify age, smoking history, current medication use, and medical background. To avoid any potential for investigator-selection bias, inclusion of the subjects was based solely on age and smoking history.

Subjects who met the following criteria were excluded: history of asthma, any respiratory disorders other than COPD, received antibiotics for lower respiratory infection in the past 6 weeks, received systemic corticosteroids in the last 4 weeks, receiving β-blockers, known hypersensitivity to salbutamol, and history of tachyarrhythmia.

Eligible subjects were scheduled for a morning clinic visit and instructed to refrain from using short-acting bronchodilators for 6 hours, long-acting bronchodilators for 12 hours, theophylline for 24 hours, caffeine-containing beverages and foods for 6 hours, strenuous exercise for 12 hours, and smoking for 30 minutes before the visit.

Written informed consent was obtained from all participants before investigations were performed at the clinic visit. The protocol was approved by the Institutional Review Board Services, Ontario, Canada.

Demographic information and medical history were collected and a physical examination was conducted. Subjects completed a self-administered clinic assessment questionnaire and the SGRQ ([11]) prior to the spirometric tests. Spirometry was performed using a brass Fleisch-type pneumotach (KoKo, Louisville, CO, USA) in accordance with the American Thoracic Society (ATS) criteria for acceptability ([29]). Post-bronchodilator spirometry was conducted following inhalation of 200 μ g salbutamol via metered-dose inhaler with spacer. Test results were expressed as a % of the predictive values using prediction equations from Crapo ([12]). In this study, forced vital capacity in 6 seconds (FVC₆) and forced expiratory volume in 6 seconds (FEV₆) were used synonymously. In order to standardize the spirometric results, we used the minimum of 6 seconds for the measurement of FVC₆ (FEV₆) to ensure optimal exhalation. FEV₁/FVC₆ (FEV₁/FEV₆) ratio was measured given the finding from Swanney et al. ([13]) that FEV₆ is an accurate, reliable alternative to FVC for diagnosing airway obstruction and that FEV₆ is reasonably comparable to FVC for the spirometric diagnosis of restriction.

Subjects with a normal pre-bronchodilator spirometry (FEV₁/FVC₆ ≥ 70% and FEV₁ of > 80% of the predicted value) did not undergo bronchodilator challenge testing. These subjects were subsequently categorized according to their pre-bronchodilator spirometry into either normal (without chronic respiratory symptoms) or stage 0 (with chronic respiratory symptoms). All subjects with a pre-bronchodilator FEV₁/ FVC₆ < 70% underwent a bronchodilator challenge test and the diagnosis of COPD was confirmed in the presence of a post-bronchodilator FEV₁ of < 80% predicted value in combination with an FEV₁/ FVC₆ < 70% and were classified according to the GOLD criteria (Figure 1) ([8]). The degree of reversibility in these heavy smoking subjects did not preclude their classification into COPD GOLD categories as long as post-bronchodilator FEV₁ was less than 80% predicted ([8]).

Figure 1 Patient stratification based on Global Initiative for chronic Obstructive Lung Disease (GOLD) Classification of COPD severity.

Chronic respiratory symptoms were defined as cough and sputum production on most days for at least 3 months in a year, for at least 1 year. Normally this definition stipulates that the subject must have chronic respiratory symptoms for at least 2 consecutive years. However, a shorter time-frame was used in this study in order to recruit symptomatic subjects with predominantly early disease.

Test results were discussed with participants, as was educational information about COPD, including causes, symptoms, and possible outcomes. Referral options for treatment and the benefits of smoking cessation were also explained.

Statistical methods

Analysis of variance was used to compare the continuous data across GOLD stages for the total population. Orthogonal contrasts were performed to compare stages 0, I, II, and III with subjects classified as normal (i.e., subjects with no evidence of COPD according to the GOLD guidelines). The 95% confidence intervals for SGRQ continuous data were calculated using the Student's t-distribution. To compare proportions, chi-square tests and Fisher's Exact Tests were employed. All analyses were conducted using SAS software version 8.02.

RESULTS

Demographic information

A total of 49 advertisements were placed in a commuter newspaper over a period of 7 months. From these, 846 subjects responded by speaking to study staff or by leaving a telephone message. The majority of responders completed the TSQ (74%) with the remainder lost to follow-up after 3 telephone attempts. Of these, however, 29% (n = 244) attended the clinic visit to complete the study. Further details of exclusion of responders are shown in Figure 2.

Figure 2 Study population: details of exclusion of telephone responders.

Demographic information according to gender is shown in Table 1. Men and women were well matched, although men were heavier smokers than women (49.0 ± 26.0 vs. 35.4 ± 14.5 pack years [PPY], respectively; p < 0.0001). On average, the subjects started smoking at 17.9 ± 5.6 years of age. The stage 0 patients were younger than any of the other COPD severity groups (p < 0.0005), including normal subjects (55.5 ± 5.4 years vs. 59.6 ± 7.2 years; p = 0.0005) (Table 2). The frequency of current smoking in stage 0 subjects (80.0%) was significantly greater than in those in the normal category (33.0%; p < 0.0001), despite very similar PPY histories. Compared with normal subjects, PPY was significantly higher for stage II subjects (p = 0.0045), but not for stages I and III. Although it appeared that men had a greater frequency of stage II disease than women, the difference was not statistically significant (18.6% vs. 11.5%; p = 0.1553). Current smokers were on average 4 years younger than ex-smokers, but had a longer duration of smoking and higher PPY. Mean % predicted FEV₁, however, was similar within each COPD classification, regardless of current smoking status.

Table 1 Demographic characteristics and smoking history by gender^a

	Total	Male	Female
N (%)	244	140 (57.3)	104 (42.6)
Age (years)	59.4 ± 7.5	59.4 ± 7.5	59.4 ± 7.4
BMI (kg/m^2)	26.5 ± 5.3	26.3 ± 4.2	26.6 ± 6.4
Current smoker	138 (56.6)	82 (58.6)	56 (53.8)
PPY^b	43.2 ± 22.8	49.0 ± 26.0	35.4 ± 14.5
Duration of smoking (years)	34.9 ± 10.4	35.1 ± 10.7	34.7 ± 9.9
FEV1 (% pred.)^c	87.4 ± 18.6	83.8 ± 19.3	92.3 ± 16.3
FEV1/FVC6 ratio^c	71.8 ± 8.1	70.7 ± 8.5	73.2 ± 7.3
Cough and sputum present	112 (45.9)	70 (50.0)	42 (40.4)
COPD GOLD Stage
Normal	91 (37.3)	51 (36.4)	40 (38.5)
Stage 0	65 (26.6)	36 (25.7)	29 (27.9)
Stage I	43 (17.6)	21 (15.0)	22 (21.1)
Stage II	38 (15.6)	26 (18.6)	12 (11.5)
Stage III	7 (2.9)	6 (4.3)	1 (1.0)

BMI = body mass index. PPY = pack years. FEV₁ = forced expiratory volume in 1 second. FVC = forced vital capacity. COPD, chronic obstructive pulmonary disease. GOLD, Global Initiative for Chronic Obstructive Lung Disease. ^aData are presented as n (%) or mean ± SD. ^bPPY significantly higher for males than females (p = 0.0001). ^cPre-bronchodilator.

Table 2 Demographic characteristics by Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification^a

	Normal	Stage 0	Stage I	Stage II	Stage III
Total N = 244 (%)	91 (37.3)	65 (26.6)	43 (17.6)	38 (15.6)	7 (2.9)
Males	51 (56.0)	36 (55.4)	21 (48.8)	26 (68.4)	6 (85.7)
Females	40 (44.0)	29 (44.6)	22 (51.2)	12 (31.6)	1 (14.3)
Age (y)	59.6 ± 7.2	55.5 ± 5.4	61.9 ± 8.6	62.0 ± 7.1	62.9 ± 8.4
BMI	25.9 (17.6–39.5)	25.8 (17.0–53.6)	24.4 (18.4–39.3)	25.3 (19.0–50.7)	23.4 (18.4–34.3)
PPY	40.3 ± 23.3	39.9 ± 18.8	44.1 ± 21.1	52.7 ± 24.7	53.3 ± 36.1
Duration of smoking^b	31.2 ± 9.6	34.8 ± 7.9	36.5 ± 12.4	41.3 ± 9.5	39.4 ± 12.9
FEV1 % predicted^c	95.9 ± 12.1	95.8 ± 12.5	93.0 ± 10.0	67.8 ± 8.3	42.7 ± 7.0
FEV1/FVC6 ratio^d	76.2 ± 3.9	77.0 ± 4.2	66.1 ± 3.3	62.1 ± 6.6	52.6 ± 7.7
Cough and sputum present	0	65 (100)	18 (41.9)	25 (65.8)	4 (57.1)

GOLD = Global Initiative for Chronic Obstructive Lung Disease. BMI = body mass index. PPY = pack years. FEV₁ = forced expiratory volume in 1 second. FVC = forced vital capacity. ^aData are presented as n(%) or mean+SD, median and range are presented for BMI. ^bDuration of smoking is reported in years. ^cFEV₁is pre-bronchodilator for normal subjects and stage 0 and post-bronchodilator for stages I, II, and III. ^dFEV₁/FVC₆ values are pre-bronchodilator.

COPD frequency in this pilot study

Stratification of subjects according to the GOLD criteria revealed that there were 91 (37.3%) normal subjects (i.e., without COPD) and 153 (62.7%) subjects with COPD. There was no difference in mean % predicted pre-bronchodilator FEV₁ between normal individuals (95.9%) and stage 0 subjects (95.8%) (Table 2). Mean % predicted post-bronchodilator FEV₁ was for stage I (93.0%), for stage II (67.8%) and for stage III (42.7%). There were no subjects in stage IV. The frequency of COPD in this population with abnormal spirometry (defined by an FEV₁/FVC₆ ratio of < 7 % predicted) was 36% overall, 23% for current smokers and 13% for ex-smokers.

Previous diagnosis of COPD

Mean % predicted pre-bronchodilator FEV₁ was 88% for stage I, 63% for stage II and 39% for stage III. Previous diagnosis of COPD had been made in 17% of those classified as stage 0, 19% of stage I, 34% of stage II and 86% of stage III (Figure 3). Previous spirometry testing was reported by 26% of all participants. For those with the more severe stages (II and III), the proportion was 47%.

Figure 3 Percent of patients with previous diagnosis of COPD stratified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Classification of COPD severity.

Use of inhaled medications

In total, 33 (14%) of the subjects had been prescribed one or more inhalers. When stratified by GOLD, the % of subjects on short-acting bronchodilators (SABA) was: Normal (3%), stage 0 (5%), stage I (21%), stage II (29%), and stage III (43%). Subjects on inhaled corticosteroids (ICS): stage 0 (6%), stage I (9%), stage II (4%), and stage III (29%). Subjects on long-acting β-agonists (LABA) included: stage I (5%), stage II (3%), and stage III (14%). When stages II and III were combined, 33% were on one or more inhalers and of this group, the percentage of subjects on SABA, ICS, and LABA were 31%, 13%, and 4%, respectively.

Chronic symptoms

Chronic cough and sputum production were present in significantly more smokers (64.5%) than ex-smokers (21.7%; p < 0.0001). There was a trend towards a significant difference in the proportion of stage I subjects with cough and sputum production compared with stage II and III subjects with cough and sputum production (42% vs. 64%, respectively; p = 0.05).

Health status/quality of life

223 completed the SGRQ and 21 subjects (9%) refused. Mean age and smoking history among this sub-population did not differ from those for all participants in the study. In the SGRQ, a lower score indicates a better patient perceived quality of life, while a higher score represents a more severe impairment in health status.

The mean symptom domain scores for normal subjects were significantly better than all GOLD stages (stages 0, II, and III, p < 0.0001; for stage I, p = 0.0011) (Table 3). The mean impact scores were also significantly better in normal subjects than in all COPD GOLD stages (p < 0.0001), except for stage I (p = 0.1932). Compared to normal individuals, activity scores were not different in stages 0 and I (p = 0.0189 and p = 0.7162 respectively); however, these scores were significantly worse in stages II and III disease (p < 0.0001). There were significant differences in the SGRQ total scores between normal subjects and all COPD GOLD stages (p < 0.0001) except for stage I (p = 0.1409) (Figure 4). When the total scores in stage I subjects were stratified by presence/absence of chronic cough and sputum production, those with symptoms had worse scores than normal subjects (n = 17 with symptoms had a total score of 21, p = 0.0065; n = 19 without symptoms had a total score of 15, p = 0.59). Symptomatic subjects with stage I and II COPD had worse SGRQ total scores than asymptomatic subjects with the same severities of COPD (p < 0.0003 and p < 0.0001, respectively). There were too few subjects with stage III COPD to compare SGRQ total scores in those who were symptomatic or asymptomatic).

Figure 4 St. George's Respiratory Questionnaire (SGRQ) Total Score stratified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Classification of COPD severity (N = 223). p values for comparison of mean SGRQ Total Scores to normal subjects.

Table 3 SGRQ domain scores by GOLD classification^a

Subjects	Total score	Activity score	Impact score	Symptom score
Normal	12.7 (9.9, 15.5)	22.9 (18.4, 27.4)	6.9 (4.5, 9.3)	10.3 (7.5, 13.1)
Stage 0	25.8^c(20.8, 30.7)	31.8 (25.9, 37.7)	18.1^c(13.4, 22.8)	36.1^c (30.1, 42.1)
Stage I	17.6 (12.2, 23.0)	24.5 (16.4, 32.6)	11.0 (6.5, 15.5)	24.0^b (16.9, 31.1)
Stage II	33.9^c (27.2, 40.6)	42.2^c (34.5, 49.9)	26.0^c (19.3, 32.7)	41.4^c (32.6, 50.2)
Stage III	50.8^c (30.9, 70.7)	67.1^c (45.9, 88.3)	40.7^c (21.6, 59.8)	50.9^c (21.8, 80.0)

SGRQ = St. George's Respiratory Questionnaire. GOLD = Global Initiative for Chronic Obstructive Lung Disease. ^aData are presented as mean and 95% confidence intervals. Significance level was set at 0.01 to adjust for the multiple comparisons. SGRQ scores for each level of the GOLD classification were compared to normal subjects; those scores significantly worse than Normal subjects scores are indicated as follows: ^b p = 0.0011; ^c p < 0.0001.

DISCUSSION

This pilot study revealed that subjects with normal lung function who report chronic respiratory symptoms of cough and sputum production, experience a significant burden of illness which has not been previously reported. Prior to our study, it was unknown whether the initial stages of COPD defined by the GOLD classification had any meaningful impact on the quality of life measures. Although FEV₁ is a useful indicator for diagnosis and prognosis of COPD ([14], [15]), it is not a surrogate for symptoms nor does it correlate very well with symptoms ([15]). This has led to the utilization of respiratory disease-specific health-related quality of life questionnaires, such as the SGRQ, to assess the effects of COPD on health status.

There is minimal information to indicate that GOLD stage 0 COPD represents a clinically significant disease. Our findings revealed that GOLD stage 0 subjects exhibited a significant impairment in their quality of life compared to normal individuals. This difference was present in the SGRQ symptom, impact, and total scores suggesting that chronic cough and sputum production, as a result of active smoking, were associated with respiratory distress and an overall impairment in social and psychological well-being. Thus, these results suggest that in evaluating disease burden in early stages of COPD, respiratory symptoms are more sensitive and accurate determinants of the presence of the disease than reliance on the use of lung function measurements. Although there is no absolute correlation between chronic cough, sputum, and the development of COPD, there are reports indicating a more rapid decline in FEV₁ in subjects with chronic respiratory symptoms ([16], [17], [18]). Since at present there are no other markers of COPD susceptibility in an at-risk population, stage 0 may provide an opportunity to enhance efforts for early detection, to implement smoking cessation and potentially to reduce morbidity and mortality of the disease ([19]).

The natural history of GOLD stage 0 is unknown and it is unclear whether this stage may provide any predictive value for the development of more advanced stages of COPD. Vestbo and Lange ([20]) found that GOLD stage 0 does not identify subjects for the development of COPD. In contrast, Lindberg et al. ([21]) reported that GOLD stage 0 disease appears to discern those at risk for COPD, and that chronic respiratory symptoms including cough and sputum production were related to the development of COPD. Antonelli-Incalzi et al. ([22]) suggested that health status may frequently deteriorate in GOLD stage 0 subjects possibly because of respiratory symptoms or co-existing non-respiratory-related problems. Nonetheless, there is heterogeneity of health status in these subjects and thus selected measures of quality of life might be a marker of COPD progression. Ekberg-Aronsson et al. ([23]) reported that among smoking men, stage 0 was associated with a significantly increased risk of all-cause mortality, suggesting that individuals at this stage may have a very unfavorable prognosis.

Our findings demonstrate that GOLD staging of COPD corresponds to significant differences in health status between normal subjects and all GOLD stages with the exception of stage I. Furthermore, it was unexpected that GOLD stage 0 subjects had worse health status than those in stage I. The explanation for this observation is that stage I subjects, by nature of the definition, may or may not be symptomatic and indeed many in this study did not have chronic respiratory symptoms. It is tempting to speculate that the difference between stages 0 and I may be, in part, related to functional adaptive responses. The subjects at stage I disease might become so accustomed to early respiratory symptoms that they may develop a tendency to underreport symptoms, particularly since airflow limitation at this stage would not be expected to be associated with a significant ventilatory limitation. Moreover, it is known that there is a weak correlation between FEV₁ and health-related quality of life. Our results suggest that the spirometric classification of stage I may not provide the most clinically relevant assessment of disease burden. We therefore question whether the GOLD definition of stage I in asymptomatic subjects has any predictive value for a clinically significant disease and why GOLD stage 0 should be removed, given the potential future burden of symptomatic patients.

General population surveys in Europe and North America ([14], [21], [24], [25], [26], [27]) have reported COPD prevalence rates of 5–15%, with smoking rates ranging from 12% to about 50% ([5], [24], [28]). In this study, the GOLD classification resulted in the addition of 27% of stage 0 and 18% of stage I subjects that yielded a COPD frequency of 63%. The GOLD classification defines early disease by incorporating chronic respiratory symptoms with normal pulmonary function and characterizes early airway obstruction as FEV₁/FVC₆ < 70%. Other studies have used FEV₁ < 80% predicted and did not include chronic respiratory symptoms in the COPD staging criteria. Thus, the higher frequency found in this study was both due to the addition of GOLD stages 0 and I and to a population that consisted entirely of heavy smokers and ex-smokers.

Given that our objective was to identify early disease, chronic symptoms were defined as the presence of cough and sputum production for at least 3 months for a minimum of 1 year rather than the standard definition of 2 years. This may have led to an overestimation of the frequency of GOLD stage 0 in this population. However, even if stage 0 subjects were excluded, 36% had objective evidence of airway obstruction. Takahashi et al. ([6]) conducted a similar study in subjects ≥ 40 years old and reported airway obstructive changes (FEV₁/FVC₆ < 70%) in 27% of all analyzed participants.

Despite the current guidelines ([1], [8]), this study found a significant under-utilization of spirometry in symptomatic heavy smokers and those with advanced stages of COPD. In fact there are data ([11]) that highlight how spirometry is under-utilized in the primary care setting. With limited access to spirometry, and in view of the time and cost constraints of SGRQ administration in a busy primary care practice, a simple symptom assessment tool such as a short respiratory questionnaire should be used for early detection of COPD.

Our results revealed that medical therapy for COPD was not appropriate for the severity of the disease and, mostly, did not adhere to current guidelines. This may reflect under-diagnosis of the disease combined with the lack of a standardized method of classifying disability in most stages of COPD. At the present time, there is insufficient data describing the benefits, if any, on the pharmacologic management of GOLD stage 0 disease. Our finding of a significant impairment in quality of life in this stage highlights the importance of the need for clinical studies to further evaluate the therapeutic needs of such patients and whether treatment initiated at this early stage may influence the natural history of COPD.

There are limitations associated with this study. Most notably, the subjects were self-selected; the study was conducted in only one metropolitan location and it targeted an urban population who had a significant history of smoking. The advertisements ran in a commuter newspaper, limiting enrolment of potential subjects primarily to those who have access to public transportation. It is also conceivable that those responding to the advertisements were more symptomatic and therefore motivated to investigate the effects of smoking on their lungs. Consequently, individuals with chronic symptoms may tend to be over-represented in this sample.

In contrast, subjects with more advanced disease or those on adequate treatment may not have responded, feeling that participating in a study was an added burden. Furthermore, asymptomatic individuals or those who were functionally impaired by the disease may have felt that an assessment was simply not necessary. Given our focus on stage 0 disease, it is possible that using a younger cut-off age would have allowed us to identify more subjects at risk for COPD. Also, not performing post-bronchodilator spirometry on stage 0 subjects may have led to asthmatics being included in this group. In addition, the withdrawal rate was very high and nearly half of those booked for a visit did not attend the clinic. This creates a potential bias in the population assessed in this study. The small sample size of this pilot study also limits the generalizability of these results to larger populations.

One challenge with early diagnosis of COPD is discerning COPD from other conditions with similar symptoms such as asthma, congestive heart failure, bronchiectasis and carcinoma of the bronchus. Further, many of these conditions can co-exist with COPD, particularly those associated with cigarette smoking. Although a chest X-ray is recommended to exclude many of these differential diagnoses, key factors such as age, smoking status and pack years, symptoms (cough, phlegm, dyspnoea, wheeze), and prior diagnosis consistent with asthma or COPD can help to discriminate between persons with and without COPD.

In conclusion, COPD at GOLD stage 0 was largely under-diagnosed in this population at risk for the disease. These subjects demonstrated significant impairments in their quality of life measures mainly due to the presence of chronic cough and sputum production. Thus, assessment of chronic respiratory symptoms may be a more sensitive indicator of early disease than evaluation of lung function by spirometry. Since stage 0 subjects were younger and mostly active smokers, detection of the disease at this stage may provide a unique opportunity for early intervention and initiating a smoking cessation programme. Large, prospective, population-based studies are needed to validate the natural history of GOLD stage 0 and to assess the impact of early disease on the global burden of COPD.

Presented in poster form at the 2002 American Thoracic Society meeting, Atlanta, Georgia, USA, and 2002 European Respiratory Society Meeting, Stockholm, Sweden.

This study was supported by a grant from Boehringer Ingelheim (Canada) Ltd./Ltée and Pfizer Canada. The authors thank Dr. Paul Jones for his review and helpful comments during the preparation of the manuscript. Institution where this work was performed: Pulmonary Care Clinic, 984 Bay Street, Suite 501, Toronto, Ontario, Canada, M5S 2A5