The SEPAR-ALAT guidelines define chronic obstructive pulmonary disease (COPD) as the presence of chronic airflow obstruction that is not reversible (reduction of forced expiratory volume in one second [FEV1] and the FEV1/forced vital capacity [FVC] ratio) mainly caused by an inflammatory reaction to tobacco smoke.1 This definition, which does not substantially vary from that proposed by GOLD2 or by the ATS-ERS,3 poses operative problems that limit its usefulness in clinical practice as it is based on an arbitrary cut-point whose clinical relevance has not been properly evaluated. The main advantage of using such a simple criterion is that it can contribute to the diffused use of spirometry, especially in the primary care setting, and that it reduces the confusion of recent years for establishing the diagnosis of COPD, especially in the less severe forms.

Without a doubt, the use of an FEV1/FVC ratio less than 70% can reduce this discrepancy, but it is necessary to recognize its limitations as this cut-point varies with age and height. It may therefore incorrectly classify the presence of obstruction at extreme ages.

As in other diseases, the prevalence of COPD can be conditioned by the criterion that is used to establish its diagnosis. With the use of the fixed ratio, there may be a high number of COPD overdiagnoses in healthy subjects who are older or tall, and the opposite may be true in short young subjects.4,5 The risk for overdiagnosis is especially relevant in patients over the age of 70. In a study by Hardie et al.6 of healthy non-smoker seniors, it was demonstrated that 35% of subjects over the age of 70 presented an FEV1/FVC ratio of <70%; this prevalence reached 50% if they were over the age of 80. At the other extreme, young patients in whom early detection can be relevant could be considered normal using the GOLD criteria.

In order to avoid these limitations, some authors recommend the use of the lower limit of normal (LLN).7,8 This posture has been recently supported by the ATS/ERS guidelines for interpreting spirometry, which recommend the use of the LLN to diagnose obstruction.9 Although it is founded on statistically solid concepts, this cut-point originates in cross-sectional or database studies but, from a clinical standpoint, their clinical relevance has not been clearly established compared with the GOLD criteria. Without this information, it is essential to be aware of any discrepancies derived from using one or the other criterion, as this can condition important differences, both from a clinical as well as from an epidemiological perspective.

Based on a cohort of patients diagnosed with COPD by the GOLD criteria, we analyzed the characteristics of the patients diagnosed with COPD by the LLN criterion and compared the population excluded by this criterion with a non-COPD control group.

23.2% (232/970) of the “overdiagnosed” patients with the GOLD criterion compared with the LLN presented a profile similar to the COPD cases diagnosed by LLN for the number of exacerbations that required hospital care, pharmacological treatment and associated cardiovascular disorders.

Table 1 presents the main characteristics of the 3 study populations. Out of the 970 patients selected, 1.35% were GOLD stage 1, 38.2% stage 2, 49.5% stage 3 and 11% stage 4. Only 738 (76%) of the subjects studied presented obstruction by the LLN criterion. When COPD was defined by the LLN criterion, patients were identified with a greater functional deterioration that the non-LLN GOLD population. The patients with COPD by the LLN criterion presented significantly lower FEV1/FVC values (0.55 [0.8] vs 0.66 [0.2], P=.000), FEV1% (44.9% [14] vs 53.8% [13], P=.0000) and FVC (64.7% [17] vs 70.4%, P=.04).

The 2 COPD groups presented a greater frequency in ER visits in the previous year (57% and 52% of the patients, respectively, compared with 11.9% of the control group), without there being any statistically significant differences between the two. This same pattern was observed in the number of visits to the ER in the last year: 1.98 (1.6), 1.84 (1.5) and 1.18 (0.7), respectively. Nor were there significant differences between the two groups of patients in the number of hospitalizations due to COPD: 1.1 (0.4) and 1.09 (0.49), respectively.

Table 2 demonstrates that when we analyze the prevalence of the comorbidities that are most frequently associated with COPD there is, compared with the control group, a clear increase in the percentage of patients with COPD who present associated disorders. These differences, however, were not very relevant between the two COPD groups and were only significant for ischemic heart disease.

Table 3 presents the pharmacological prescription profile of the patients with LLN criterion and in the patients who were not classified as COPD by the LLN criterion. Short-acting bronchodilators were excluded as their occasional use is frequent in many intercurrent processes that cannot always be catalogued as COPD. The prescription profile is similar in both patient groups for the main bronchodilator and anti-inflammatory drugs.

When we analyzed the consumption of drugs related with the treatment of the main cardiovascular disorders, the consumption of medication among COPD patients was clearly higher than in the control group, but with hardly any differences between both patient groups.

The main conclusion of this study is that, in standard clinical practice, the use of LLN for defining COPD excludes a large number of patients when compared with the GOLD criteria. This group of patients that was excluded by the LLN criterion presents important clinical manifestations and a high consumption of health-care resources, both in care provided as well as medication. These data suggest that before applying the LLN criterion, it is necessary to clarify which factors are implicated in the clinical deterioration of these patients, the reasons for why there is a high consumption of drugs related with COPD in a group that would not be identified as COPD when using the LLN criterion, and if the origin of its clinical deterioration is primarily pulmonary or whether it is associated with diseases apart from the pulmonary pathology.

In recent years, many initiatives have been aimed at obtaining a fast diagnosis and early treatment of COPD. Regarding the use of the FEV1/FVC ratio, its simplicity may favor its implementation in clinical practice and facilitate early diagnosis of the disease, although its clinical relevance has not been well established. This is especially true in GOLD stage 1, where there may be great discrepancies with other criteria based on statistical concepts such as the LLN. In an attempt at improving diagnostic precision, it has been proposed to use the FEV1/FVC ratio together with an FEV1 value below 80%, which would exclude GOLD stage 1. Nevertheless, this proposal is also not free from controversy, as even in this stage the presence of symptoms, reduced exercise capacity and increased mortality have been demonstrated.12–17 Furthermore, the greater or lower relevance of using this criterion could also be conditioned by age.8

Currently, there is a body of opinion that encourages the use of LLN for establishing the diagnosis of COPD. Supporting this posture, it has been reported that the ratio would incorrectly overdiagnose older patients as COPD. Another argument in favor of the use of LLN is that it would enable the disease to be detected early on in relatively young populations, which is where it is essential to introduce preventive measures to keep the disease from progressing further and to detect it in advanced phases. However, there are no studies that demonstrate that earlier detection in young subjects using LLN has a real impact in the disease evolution or load. Finally, to those who defend the use of FEV1/FVC over LLN based on its simplicity, an argument could be made that this aspect may be of little relevance because even the most basic current devices are able to incorporate the calculation of LLN, and the GOLD classification requires the use of theoretical values to establish severity levels.18

On the other hand, there are also arguments in favor of using the FEV1/FVC ratio because it is able to establish a limit of functional normality, regardless of the degenerative changes that occur with age, and thus this limit would be clinically transcendent, regardless of age.19 This standpoint assumes that the changes that occur with age do not necessarily reflect a situation of normality. This posture would be important if these changes required specific interventions, as in the case of the loss of eyesight. In practice, presbyopia could be considered normal in an age-adjusted statistical model; but, if a set limit of normality is used, it is possible to detect a problem and indicate a treatment, regardless of whether its presentation is practically universal as we age. However, in lung function these postures are theoretical and there are no consistent arguments that demonstrate their usefulness in clinical practice. For this reason, aside from theoretical considerations, the use of a certain criteria for establishing the diagnosis of COPD should be based on its clinical relevance and not on aspects of apparent simplicity, which may be easily resolved with current technology.

The results of this study do not establish which criteria is better, but they do clearly indicate that with the use of the LLN criterion there is a high percentage of patients who would be excluded from the diagnosis. These patients make up a population that has important clinical manifestations and a high consumption of health-care resources, with a clinical profile similar to other COPD patient groups that is very different from the control population. There are many possible factors that influence this situation, and they are not always related with airflow obstruction (associated diseases, weight problems, etc.) which should be specifically studied in this population type.20–23 Until we have this information, the patient should be assessed by the clinician, but the use of a criterion like LLN would exclude from the start an important population that, due to the consumption of health-care resources that it represents, requires proper medical evaluation.

It is also necessary to establish which criterion is best from an epidemiological standpoint.24 Aside from the marked discrepancies in the prevalence of the disease that there may be (depending on the criterion used) any analysis that tries to establish a relationship between COPD and other processes (e.g. vascular disease) should be based on a criterion that is not arbitrary. In our series, the use of LLN did not improve the results that had been previously obtained in the ARCE study.25 In that study, which included a smaller population and did not have a control group, the use of the LLN did not substantially modify the results obtained with GOLD when evaluating the association of COPD with vascular disorders. In this current study, using the LLN criterion, we have found a greater prevalence of ischemic heart disease in the COPD group, but there were no significant differences for other cardiovascular risk factors, cerebrovascular lesions or peripheral vascular lesions. The complexity of COPD, with different patient profiles for one same functional loss, complicates relationships of this kind, be it with either the GOLD or LLN criteria.

The main limitation of our paper was that it is a cross-sectional study, and the data should therefore be confirmed by longitudinal studies. Although such an approach would be ideal, it would entail a great delay, and while waiting for the results to be in possibly a high number of patients with important clinical affectation would be excluded from a proper assessment if the LLN criterion were used.26

Another limitation is that the population of this study was made up of patients seen in the pulmonology and primary care departments due to respiratory symptoms. Therefore, the results cannot necessarily be extrapolated to the general population. Nevertheless, in a population-based study, García-Rio et al.27 also observed no differences between the 2 groups for respiratory exacerbations, distanced walked in the 6-min walk test or in systemic biomarkers.

Last of all, it is possible that, by selecting the sample from patients with COPD diagnosis using the GOLD criteria, short young patients with mild COPD may have been excluded. This aspect may be relevant in early detection programs, but it is not very important in daily clinical practice. The mean ages of the COPD groups were 63 and 66, similar to the age reported in other series using the characteristics of patients with COPD seen in primary specialized care consultations.28

In conclusion, the use of LLN as a criterion for establishing COPD diagnosis, compared with the GOLD criterion, excludes a high number of patients with important symptoms and a high consumption of health-care resources. Before applying this concept in clinical practice, it is necessary to analyze in detail the population group that was excluded and to determine which factors are associated with the symptoms and the high consumption of health-care resources.

This study has been funded by Esteve Laboratories.