Misidentification of airflow obstruction: prevalence and clinical significance in an epidemiological study
Int J Chron Obstruct Pulmon Dis. 2015 Mar;10:535-40.
Pothirat C, Chaiwong W, Phetsuk N, Liwsrisakun C.
Author affiliations: Division of Pulmonary, Critical Care and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Background: The fixed threshold criterion for the ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) <0.7 is widely applied for diagnosis of airflow obstruction (AO). However, this fixed threshold criterion may misidentify AO, because thresholds below the fifth percentile of normal FEV1/FVC (lower limit of normal; LLN) vary with age. This study aims to identify the prevalence of AO misidentification and its clinical significance.
Materials and methods: A cross-sectional population-based study was conducted to identify the prevalence of chronic respiratory diseases in adults older than 40 years of age who live in municipal areas of Chiang Mai province, Thailand. All randomly selected subjects underwent face-to-face interviews and examinations by pulmonologists, and received chest radiographs and post-bronchodilator spirometry. AO misidentification was classified into under- or overestimated AO subgroups. Underestimated AO was defined as ratio of FEV1/FVC greater than the fixed threshold, but below the LLN criteria. Overestimated AO was defined as the ratio of FEV1/FVC below the fixed threshold but greater than the LLN criteria. The clinical significance of each misidentified subject was then explored.
Results: There were 554 subjects with a mean age of 52.9±10.1 years and a percent predicted FEV1 of 85.5%±15.4%. The prevalence of AO misidentification was 5.6% (31/554), and all subjects belonged to the underestimated subgroup. Clinical significance of underestimated subjects included clinical AO disease of 22.6% (7/31) (three subjects with chronic obstructive pulmonary disease [COPD] and four subjects with asthma); chronic respiratory symptoms of 54.8% (17/31) (mostly associated with chronic rhinitis, 70.6% (12/17); and only 12.9% (4/31) were identified as non-ill subjects.
Conclusion: The prevalence of AO misidentification in this population was significant, and all were underestimated subjects. Most underestimated subjects had clinical significance as related to obstructive airway diseases and chronic respiratory symptoms, mostly associated with rhinitis.
Keywords: spirometry, airflow obstruction, chronic obstructive pulmonary disease, asthma
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (1) defines COPD as a ratio of post-bronchodilator (BD) forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) of less than 0.7 which was in agreement with both the American Thoracic Society (ATS) and the European Respiratory Society (ERS)(2). As FEV1/FVC ratio varies with age, using a fixed threshold criterion may result in over- or underestimation of COPD, especially in advancing or young age groups (3−5). GOLD guidelines also suggest defining AO by a reduced FEV1/FVC below the statistically defined fifth percentile of normal (lower limit of normal; LLN) in order to minimize potential misclassification (6). By using a different criterion for diagnosis of AO, there are two possible discordant results in reference to misidentified AO subjects. Subjects with LLN ≤ FEV1/FVC < 0.7 are identified as overestimated subjects and those with 0.7 < FEV1/FVC ≤ LLN as underestimated subjects. The most appropriate criterion to define AO remains controversial (1). Although many studies evaluate AO by using LLN criterion (7-12), only a few have attempted to determine the clinical impact of overestimated and underestimated subjects (7, 8). Here we analyze data from our population-based study to identify the prevalence of AO misidentification (over- and underestimated subjects) and explore its clinical significance.
Figure 1 Age distribution of entire study population based on sex
Subjects were invited to the pulmonary administrative office at the hospital to confirm their information by face-to-face interviews and to be physically checked by pulmonologists from the study team. Each subject underwent a chest radiograph and post-BD pulmonary function test in the form of a standard chest radiograph and standard ATS/ERS post-BD spirometry (2). Interpretation of AO in each subject was independently based on two standard criteria; fixed threshold criterion (a ratio of post- BD FEV1/FVC less than 0.7) and lower limit of normal (LLN) criterion (a ratio of post- BD FEV1/FVC below the cut-off value set at the fifth percentile of the normal distribution derived from healthy lifetime nonsmokers in Thailand) (13, 14). Classification of AO based on two criteria is shown in Table 1.
Table 1 Group definitions based on the presence of airflow obstruction (AO) according to two methods
Notes:* Fixed threshold criteria, ratio of FEV1/FVC less than 0.7
**LLN criteria, ratio of FEV1/FVC less than the fifth percentile of normal
Abbreviations: AO, Airflow obstruction; FEV1, Forced expiratory volume in first second; FVC, Forced vital capacity.
Almost half the subjects were in the middle age group (48.2%) whereas only 7.8% were elders of ≥70 years (Figure 1). Prevalence of AO increased from 5.4% (30/554) by using the fixed threshold criterion to 11.0% (61/554) by using the LLN criterion. Prevalence rates of definite AO and misidentified AO subjects were 5.4% (30/554) and 5.6% (31/554) respectively and all misidentified AO subjects belonged to the underestimated subgroup (Table 2). Most subjects in the undetermined group had chronic respiratory symptoms 17/20 (85.0%) and 12/20 (60.0%) had a diagnosis of chronic rhinitis.
Overestimated subjects could be in the early phase of the disease with the possibility of arresting further disease progression through intervention such as smoking cessation and vice versa, as well as underestimated subjects may be those with late detection that missed the chance to receive appropriate intervention to improve their quality of life and reduce consumption of healthcare resources. All of misidentified AO subjects in our study were proved to be underestimated AO because most of them were in young age group which supported earlier study that overestimated AO is frequently found in advanced age groups (8). In clinical practice, diagnosis of COPD should be based on multimodalities of evidence and not only on a single tool to achieve the highest probability. Undetermined subjects were the largest group of underestimated subjects and had clinically significant findings. Most of undetermined subjects had chronic respiratory symptoms mostly shown to have chronic rhinitis which is a well-known precedent for asthma (15). Moreover, we found approximately two-thirds of underestimated subjects had chronic respiratory symptoms and most of them were due to chronic rhinitis. If untreated, chronic rhinitis, may have a considerable financial effect and impact quality of life (16, 17). Furthermore, it is one of the most important risk factors in asthma development (18).
Table 2 Frequency by group definition according to the presence of airflow obstruction (AO) based on two methods
Note: Results are expressed as n (%).
Abbreviation: AO, Airflow obstruction
Importance of the study:
Most underestimated subjects in this epidemiological study had conditions of clinical significance, including clinical AO disease and chronic respiratory symptoms mostly associated with rhinitis. Therefore, subjects meeting the LLN but not fixed threshold criteria should not be considered as false positive AO. The LLN criterion may be considered as a useful supplementary tool for detection of possible AO in prevalence studies for a population cohort. In addition, each underestimated subject should be clinically evaluated and undergo further investigation by physicians.
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The authors wish to thank the patients who kindly took part in this study and to acknowledge staff members from the Division of Pulmonary, Critical Care and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand for their contributions to this study.
Assoc. Prof. Chaicharn Pothirat, MD., FCCP, Division of Pulmonary, Critical Care and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University. Street address: 110 Inthavaroros Rd.,Sriphum, Maung Chiang Mai district, Chiang Mai, 50200 Thailand
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