versus conventional cutoff values
As mentioned before, spirometry is required for the diagnosis of COPD by measuring persistent airflow limitation. However, there is still no consensus on the most appropriate threshold of FEV1/FVC for diagnosing airflow limitation.10-20 The GOLD
guidelines recommend the use of the fixed ratio of FEV1/FVC < 0.70 for the sake of simplicity.1 However, a growing body of literature indicates that considering the
physiological decline of the FEV1/FVC ratio with age (the FEV1 declines more rapidly with age than the FVC in normal subjects) the use of the fixed ratio may lead to overdiagnosis of COPD in elderly subjects5, 306-321 and underdiagnosis of COPD in
young adults.314-323 To avoid misclassification, the American Thoracic Society/European
Respiratory Society (ATS/ERS) recommends the use of statistically derived LLN values for FEV1/VC that are based on the normal distribution and that classify the bottom 5% of the healthy population as abnormal.249 This is particularly important in
patients with HF, given that HF is most prevalent among elderly individuals.32 Thus,
previously reported COPD prevalence rates may have been overestimated in prior studies that have used the fixed ratio of 0.7 to define COPD in patients with HF (Table 1). Although population-based studies have shown that the application of different criteria to define airflow obstruction dramatically changes the prevalence of COPD,5, 309, 310, 324-327
it is less well understood to what extent this occurs in patients with HF.169, 215
Table 3 Continued.
Author, Yr
No. Population Exclusion of
pulmonary disease Age, yrs Men, % NYHA LVEF, % FS/CS, % Definition Prevalence, % O R D O R D
Light and George,
1983281
28 Admitted with CoHF, most
with both right and left HF
History of chronic obstructive lung disease
62 ± ? 71 NA NA 46 FEV1/FVC
outside normal range (pred-1.65 SEE)
NA NA 61‡ NA NA#
Data are presented as mean ± standard deviation (SD) and percentages unless stated otherwise. Abbreviations: ATS, American Thoracic Society; BB, beta-blockers; CoHF, congestive heart failure; CS, current smokers; D, diffusion impairment; FEV1, forced expiratory volume in 1 second; FRC, functional residual capacity; FS; former smokers; FVC,
forced vital capacity; HF, heart failure; LVEF; left ventricular ejection fraction; NA, not available; No., number of patients; NS, non-smokers; NYHA, New York Heart Association; O, airway obstruction; post-BD, post-bronchodilator; R, restriction; SEE, standard error of the estimate; SVC, slow vital capacity; TLC, total lung capacity; yr(s), year(s). ^ Median
1
An incorrect diagnosis of COPD may result in unnecessary treatment for COPD with possible side-effects and adverse cardiovascular events associated with pharmaco- logical treatment for COPD and undertreatment with life-saving beta-blockers.12, 81, 82
Moreover, an incorrect diagnosis and interventions for COPD may have a considerable psychological impact on the subject and his/her family and may lead to unnecessary costs.12 Conversely, misclassifying a number of young adults already affected by
COPD as healthy, prevents early interventions that could limit disease progression. Therefore, there is a need for clear diagnostic criteria for COPD to avoid diagnostic confusion, incorrect diagnosis, and inappropriate treatment.
PFTs are also used for the diagnosis of other pulmonary function abnormalities than airflow limitation, such as diffusion impairment and restriction. Similarly, there is no consensus on how to define these pulmonary function abnormalities. Traditionally, the 80% predicted value (i.e. diffusing capacity or TLC < 80% predicted) has been used. This frequently used 80% predicted value has, however, neither statistical nor physiological validity249, 328 and may misclassify more than 20% of patients leading to
false-positive diagnosis in the elderly and underdiagnosis in younger patients.314
Limits of normal as the predicted ± 20% can only be accurate when the variance above and below the predicted regression line is proportional with the predicted value (i.e. heteroscedastic: large variance with large values and small variance with small values).314, 328 However, since this is not the case, as the scatter around the
predicted regression line is constant (homoscedastic) in pulmonary function measurements, the 80% predicted rule of thumb may lead to false-positive diagnosis in the elderly and shorter individuals with smaller predicted values and underdiagnosis
Table 3 Continued.
Author, Yr
No. Population Exclusion of
pulmonary disease Age, yrs Men, % NYHA LVEF, % FS/CS, % Definition Prevalence, % O R D O R D
Light and George,
1983281
28 Admitted with CoHF, most
with both right and left HF
History of chronic obstructive lung disease
62 ± ? 71 NA NA 46 FEV1/FVC
outside normal range (pred-1.65 SEE)
NA NA 61‡ NA NA#
(interquartile range). * Airway obstruction had resolved in 48% of patients 6 months after discharge. ** No definition for pulmonary function impairment was provided in the article. Prevalence data were extracted using the following definitions: airway obstruction, FEV1/FVC < 0.7; restriction, FVC < 80% predicted with FEV1/FVC ≥ 0.7. *** Isolated airway
obstruction: 31%; isolated restriction: 31%; mixed pulmonary function abnormalities: 15%. † After treatment for HF. ‡ Both during initial assessment and at the time that the pulmonary function of the patients was the best. # Mean diffusing capacity for carbon monoxide was within normal range.
in younger and taller patients with larger predicted values.314, 328 Misinterpretation of
PFT results may lead to incorrect diagnosis of disease in elderly patients with HF and as a consequence unnecessary treatment. Moreover, results may be interpreted as having more severe or unstable HF due to the effects of HF on pulmonary function and as a result unnecessary intensified treatment for HF. Finally, misdiagnosis may interfere with interpretation of research aiming to understand the impact of HF and several clinical variables on pulmonary function.329, 330 To avoid misclassification, ATS/
ERS guidelines249 again recommend the use of the fifth percentile LLN values, which
are calculated by subtracting 1.64 times the residual standard deviation (RSD) from the predicted value. However, studies using the LLN values to assess the prevalence of pulmonary function abnormalities and their predictors in patients with HF are lacking.