Nipping it in the bud: An inspiring mission for prevention and management of COPD
State Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical College, Guangzhou 510120, China
Editorial
Nipping it in the bud: An inspiring mission for prevention and management of COPD
State Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical College, Guangzhou 510120, China
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J Thorac Dis 2012;4(2):102-105. DOI: 10.3978/j.issn.2072-1439.2012.03.16
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An epidemiological survey in China revealed that the prevalence of chronic obstructive pulmonary disease (COPD) was 8.2% among Chinese adults aged 40 years or older (12.4% in men and 5.1% in women) (1). Of the patients surveyed, up to 70.7% suffered from mild (stage I) or moderate (stage II) condition, and were almost free of dyspnea (including exertional dyspnea), or with unspecific symptoms like chronic cough and sputum which were readily neglected. As a result, only 35.1% of these COPD patients had ever been diagnosed, contributing to a rate of detection far below the actual prevalence in the country. Furthermore, of any given COPD stage, less than 25% of the patients ever sought medical attention. These added up to the underdiagnosis and undertreatment of COPD in China and in other parts of the world (2-4). It is not unusual in clinical settings that a COPD patient seeks treatment only when he or she frequently feels dyspneic on exertion or even at rest. In these patients, at least 50% of lung capacity as measured by predicted forced expiatory volume in 1 second (FEV1) has been destroyed (5), and the best chance for intervention is lost. So why not move upstream the management of COPD as we do for hypertension, coronary heart disease, and diabetes mellitus - starting interventions against elevated blood pressure, dyslipidemia or hyperglycemia despite the clinically silent disease? To date, global control of COPD is lagging far behind what have been done for other chronic diseases, resulting in poor intervention/treatment outcomes and high rates of mortality and morbidity.
Mechanisms underlying the pathogenesis of COPD are yet to be fully elucidated. Due to the following aspects, research on early intervention of this disease remains extremely challenging.
Firstly, we lack sensitive and specific indicators or markers for early diagnosis of COPD. Histological study of surgically resected lung tissue from 159 patients has identified evidences of airway-wall thickening, as reflected by increased volume to surface area (V:SA), even in stage I COPD where the patients' FEV1 can still be well above 80% of predicted value (6). Exploration of biomarkers for early detection of COPD, such as serum C-reactive protein (CRP), surfactant proteins D and A (SP-D and SP-A), Clara cell proteins (CCPs), tumor necrosis factor-α (TNF-α), interleukins (IL-8, 13 and 32), granzyme B, elastin, chemokine receptor CXCR3, chemokine (C-C motif) ligand 5 (CCL5), brain natriuretic peptide (BNP), vascular endothelial growth factor (VEGF), and chitinase-like protein YKL-40, has been attempted. While these biomarkers may be useful in determining an acute exacerbation, staging and severity assessment of COPD, none of them appears competently sensitive for an early diagnosis.
In the domain of imaging studies, some authors proposed
using airway-wall thickness and severity of emphysema to
determine early-stage COPD. In a study by Ley-Zaorozhan et al., volumetric CT datasets which allow for 3D-segmentation
and skeletonization of the airways were successfully employed
to measure the inner and outer diameters of bronchi at any
given site (7). Using hyperpolarized 3helium (3He) diffusion
MRI, Fain et al. (8) detected early signs of disordered diffusing
capacities in heavy smokers whose lung function was largely
normal. These encouraging attempts shed light on the promising
role of radiographic techniques in early identification of airwaywall
thickness and emphysema. Lung function test remains so
far central to diagnosis of COPD, because of its involvement
in the "gold-standard" criteria (post-bronchodilator FEV1/
FVC<0.70) developed by GOLD (Global initiative for chronic
Obstructive Lung Disease). As we know that the ratio of FEV1/
FVC in healthy population may decrease with aging (9), the
plot then thickens - using this spirometry-based criteria would
lead to under-diagnosis of COPD in subjects aged below 50
and misdiagnosis in those aged above 50 years old (10). As
an alternative, Enright et al. suggested using the lower limit
of the normal range (LLN) as defined by the fifth percentile
of FEV1/FVC in a healthy reference population to minimize
misdiagnosis of COPD in the elderly (11). Yet this may not
mean a perfect solution. The use of LLN worldwide necessitates
the availability of population-specific reference equations
which are not established in many parts of the world (12). In
addition, staging of COPD based on reduction in FEV1 does
not correlate well with quality of life, 6-minute walk distance
and frequency of acute exacerbation (13). Nevertheless, using
FEV1/FVC<0.70 can be considerably valuable in diagnosis of
asymptomatic COPD. Following this logic, among the 70% of
patients who were with symptom-free COPD as we mentioned
at the beginning of this paper, measurement of FEV1 should
have identified majority of the subjects at the early stage of
this disease. Measurement of expiratory peak flow (PEF) as a
simple, effective and affordable diagnostic tool may also provide
some help for early diagnosis and management of COPD.
Such a strategy was adopted in a recent study where a cohort
of community residents was screened for peak expiratory flow
(PEF) with portable peak flow meter. Those with PEF below
normal expected values were referred to a designated medical
center for further evaluation of FEV1. In this way, detection
of COPD yielded a specificity of 77% and a sensitivity of 84%
(14). Some authors endeavored to identify early-stage COPD
with cardiopulmonary exercise testing (CPET) (15). They
found that patients with GOLD stage I COPD had evidence of
lowered ventilator reserve and increased dead air-space during
incremental cycle exercise, as indicated by significantly higher
Borg scale ratings of dyspnea intensity, minute ventilation
and ventilatory equivalent for carbon dioxide compared with healthy controls. Therefore CPET may be more
sensitive than the widespread accepted lung function test in
detecting COPD. In addition, Pitta et al. (16) noted a dramatic
reduction in exercise endurance among patients with mild
COPD, suggesting that CPET can also be used in the screening.
Secondly, it has not been widely recognized among
clinicians that the annual decline in FEV1 is more rapid early
in COPD. Two clinical trials, "Towards a Revolution in COPD
Health" (TORCH) and "Understanding Potential Long-Term
Improvements in Function with Tiotropium" (UPLIFT),
demonstrated that the rate of annual decline in FEV1 over a
follow-up of 3 to 4 years was -47.0 and -49.0 mL/yr, respectively,
in patients with a baseline FEV1≥50% predicted, versus
-28.4 and -23.0 mL/yr, respectively, in those with a baseline
FEV1<30%. The findings of these studies also suggested that
early intervention may contribute to greater reversibility of the
airway. By interpreting the bronchodilator response in COPD
patients, Zhang FQ and coworkers (17) showed significantly
greater improvement in FEV1 with salbutamol nebulization in
stage I COPD patients [(197±189) mL] compared to those with
stage III [(117±103) mL] or stage IV [(168±187) mL] COPD.
They speculated that the reduced FEV1 at early stages of COPD
may be largely associated with airway smooth muscle contraction
and mucus hyper-secretion, in contrasted to airway remodeling
and obvious emphysema at later stages which give rise to poor
reversibility of the airway. In collaboration with local health
administration, Zhou YM et al. (18) implemented a program
for COPD prevention and management in a community in
Guangzhou, the largest city in southern China. The interventions
included educations on tobacco cessation and COPD control,
measures to reduce indoor and outdoor air pollutions, and
treatment with short-acting beta-agonist (salbutamol) and
ipratropium bromide. During the 4-year follow-up, the annual
rate of decline in FEV1 was significantly lower in subjects of the
intervention community than those in the control community,
particularly for high-risk individuals (occupational exposure
and smokers). Implications of this study showed that, as with
community-based programs for hypertension or coronary heart
disease, simple management can result in encouraging outcomes
for early intervention of COPD at the community level.
Thirdly, evidence-based approach to early intervention
for COPD is still lacking. While smoking cessation proves
indispensable to early intervention, about 40% of COPD patients
in China are non-smokers, and less than 20% of smokers will
develop COPD later in life. Therefore, studies looking at genetic
polymorphisms are urgently needed to identify smokers who
are most susceptible to COPD. Undoubtedly, quitting cigarettes
continues to be the most crucial intervention for smokers in
whom FEV1 declines faster than as found for healthy subjects
each year (19,20). In the case of pharmacotherapy for COPD,either inhaled glucocorticosteroid (ICS) plus long-acting
beta agonists (LABA) in the TORCH study or Tiotropium in
the UPLIFT study did not produce a statistical difference in
annual rate of FEV1 decline between patients and controls after
a 4-year treatment, though, inspiring clinical efficacy of these
medications were implied in a subgroup analysis which showed
slower FEV1 decline in subjects with stage II COPD compared
with the controls (21,22). Given this, a question naturally
follows whether stage I COPD patients, which accounted for
nearly one-fourth of the study population in these two studies,
could benefit more from the medications. Today, novel classes of
anti-inflammatory drugs, such as PDE4 inhibitors (Roflumilast
and Tetomilast) (23,24), have been developed. Notably, animal
studies have demonstrated that Tetomilast may suppress the
actions of elastase and hence the development and progression
of emphysema. Some of PDE4 inhibitors are now commercially
available, but they are approved only for moderate and severe
COPD patients. The potential benefits of these products in
patients with early-stage COPD warrant future studies.
Understandably and conceivably, scientific research should
not excessively target the mid- and late-stages of COPD at
the expense of early prevention and intervention. Physicians
can be prompted for successful examples in coronary heart
disease, hypertension and diabetes, where the strategies for
management of these diseases are placed with high priorities
on early identification, early diagnosis and early intervention.
Along with developing practices of evidence-based medicine,
it is trustworthily foreseeable that this decade will witness an
overwhelming revolution in prevention and management of
COPD. |
Acknowledgements
This paper was prepared with assistance of Dr Prof Guangqiao
Zeng, the Editorial Director of Journal of Thoracic Disease. Dr
Zeng declared no conflicts of interest therein.
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References
Cite this article as: Zhong N. Nipping it in the bud: An inspiring mission
for prevention and management of COPD. J Thorac Dis 2012;4(2):102-105.
doi: 10.3978/j.issn.2072-1439.2012.03.16
|