Does copd always progress



The mean duration of follow-up of the 6,261 persons studied was 7.9 years (with standard deviation 2.8 years), and there were 1,873 deaths. Table 1 shows the baseline demographic characteristics of the cohort. Overall, the percentages of persons with spirometric evidence of COPD were: GOLD stage 1: 16%, GOLD stage 2: 12%, GOLD stage 3 or 4: 3%, and restriction: 8%.

Table 1

Demographics and description of key variables. All figures are column percentages except for counts (n, died) and age

Abbreviations: BMI, body mass index; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; MI, myocardial infarction; RID, restrictive lung disease.

Figures 2–5 show the Kaplan–Meier survival curves based on severity of COPD, both for the entire population and stratified by smoking status. In all cases, any lung function impairment was associated with an increased risk of death.

Kaplan–Meier survival curves of all 6,261 participants age 50 and over in NHANES III, stratified by lung function impairment.

Kaplan–Meier survival curves of 2,706 never smokers age 50 and over in NHANES III, stratified by lung function impairment.

These curves were used to compute the (crude) EDRs associated with COPD that are shown in Table 2. For example, amongst smokers, the 10-year survival probability persons with no lung disease was 75%, compared with 65% for persons with COPD symptoms, 63% for stage 1, 58% for stage 2, and approximately 15% for stage 3 or 4. The associated annual mortality rate over the 10-year period for smokers with no lung disease is thus –ln(0.75)/10 = 0.0288. For stages 1, 2, and 3 or 4 COPD, the rates are 0.0462, 0.0545, and 0.1897, respectively. Thus, the EDR over the 10-year period for smokers with stage 1 COPD, compared with smokers with no lung disease, is 0.0462 − 0.0288 = 0.0174. For stages 2 and 3 or 4 COPD, the EDRs are higher, 0.0257 and 0.1609, respectively. EDRs for all 24 groups are shown in Table 2. It is important to note that these are crude EDRs, unadjusted for any possible confounding factors.

Table 2

Excess deaths rates from Figures 2–5, relative to persons with no lung disease

Group Smoking status
All Current Former Never
Normal Reference Group
Stage 0 (Symptoms only) 0.0098 0.0143 0.0128 0.0055
Restrictive lung disease 0.0174 0.0069 0.0292 0.0190
Stage 1 0.0190 0.0174 0.0223 0.0207
Stage 2 0.0310 0.0257 0.0366 0.0257
Stage 3 or 4 0.0884 0.1609 0.1484 0.0707

The EDRs implicit in the “All” group in Figure 2 of Mannino and colleagues4 are roughly one-third lower than those reported in Table 2 here. The reason is that the EDR increases with age, and the Mannino and colleagues study population was significantly younger than the population used here: unlike the present study, half their population was under age 50 at the start of follow-up.

Additional analyses (not shown) indicated that persons with COPD, compared to those without lung disease, tended to be older and male, and of course were much more likely to be smokers. It is important to note that the survival curves in Figures 2–5 were not adjusted for any of the covariates. Thus, the EDRs given in Table 2 may be confounded with the effects of these covariates. We wished to obtain an unconfounded (or pure) estimate of the EDRs or RRs associated with COPD. For this we required multivariate statistical methods, such as the Cox proportional hazards regression model.

Cox models were used to adjust for age, sex, race, education, smoking status, smoking history, weight, and major medical conditions. The variables, their various levels, and the associated relative risks of mortality are shown in Table 3.

Table 3

Relative risks from multivariable Cox proportional hazards regressions models

a Notes: The respective reference groups for these relative risks are persons who are: female, non-Caucasian, college education, aged 50–59, no lung disease, never smoker (for the first model), low pack-years (for the first three models), normal weight, and without any of the specified medical conditions. b This the mortality rate for persons in the reference group described immediately above. It is computed by setting the values of the covariates (variables) in the respective models equal to zero.

Abbreviations: BMI, body mass index; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; MI, myocardial infarction; RID, restrictive lung disease.

As expected, the relative risks associated with COPD increased with increasing severity of COPD. In all cases the relative ordering of severity was preserved in the resulting RRs. However, as can be seen, the stage 1 group had a relative risk that, in 3 of the 4 cases, was actually less than that of the reference group (stage 0), though the differences were neither practically nor statistically significant. We return to this issue in the discussion. Those with restrictive lung disease (RLD) or symptoms of COPD, but no formal diagnosis, both had uniformly increased risk of death compared with those with no lung disease.

Other analyses (not shown), using models that (a) accounted for only age, sex, and COPD, and (b) were based on different subsets of data, yielded similar results. Separate analysis of pipe and cigar smokers (not shown) revealed that their mortality risk was similar to that of smokers (RR = 1.0), and higher than that of former smokers (RR = 1.1).

Further analyses (not shown) revealed that the effect of COPD did not appear to vary by sex, race, or college education. That is, there were no significant interactions. But it did vary by age, as we hypothesized, with older persons having a lower RR than younger persons (results not shown). This was true for those with stage 2 and 3 or 4 COPD, and amongst current, former, and never smokers, with one exception (it did not hold for the former smokers with moderate COPD). We comment further on this issue in the discussion.

The last row of Table 3 shows the mortality rate for the composite baseline group: female, age 50–59, non-Caucasian, college education, no lung disease, never smoker (first model only), low pack-years of smoking (models 1–3 only), normal weight, and no other medical conditions. As can be seen, even “healthy” current smokers, with low pack-years, have a baseline mortality rate that is much higher than the never smokers (0.0103 vs. 0.0041). By comparison, we note that the corresponding annual mortality rates at age 55 for the United States female general population28 and the insured population (at time of underwriting)31 are 0.0048 and 0.0009, respectively. That is, the best group contemplated by the models is slightly better than the general population, but does not have mortality as low as the recently insured (who have additionally demonstrated normal blood work, urinalysis, and electrocardiogram).

We used the model of Table 3 to compute mortality rates for various groups of 65-year-old Caucasian males with college education, normal weight, and no medical conditions (for the smoking groups we assumed low pack-years, and for the “all” group we assumed “never smoker”). These rates are shown in Table 4.

Table 4

Mortality rates for otherwise healthy 65-year-old Caucasian males based on the models of Table 3

We computed the EDRs implicit in Table 4 by subtracting from each the US male general population mortality rate at age 65 (0.0186). The resulting EDRs are shown in Table 5. As can be seen, these are smaller than the EDRs of Table 2 for the “all”, former, and never groups, and higher for some of the smoking groups. Otherwise, there is no clear pattern. That the EDRs would differ between the tables is understandable, as the former are crude (or possibly confounded) while the latter are at least partially adjusted for the factors in the models of Table 3 (that is, computed after controlling for the factors in the models, including having no medical conditions).

Table 5

Excess death rates for otherwise healthy 65-year-old Caucasian males, computed as Table 4 less the mortality rates for males aged 65 in the general population (0.0186)

Implicit in Table 5 is the observation that the EDRs for COPD are higher for smokers than for nonsmokers or never smokers. For example, within current smokers, the EDR for stage 3 or 4 COPD compared with mild COPD is 0.0601 − 0.0109 = 0.0492 whereas for never smokers it is only 0.0010 − (−0.0077) = 0.0087. This is one example of “super-additivity”, where the risk associated with two factors (here, smoking and COPD) is greater than the sum of the separate risks associated with these factors. Super-additivity is also seen, for example, with respect to smoking and diabetes. We return to this issue in the discussion.

We next used the rates of Table 4 to compute life expectancies for the 24 (male) groups. The indicated rates were used for age 65. Because we found that the RR decreases with age (and the EDR increases with age), an assumption of constant EDR or constant RR with age was not warranted. Of course we could have used the model of Table 3 to compute mortality rates at all ages. Yet, as just noted, the RR decreases with age. Thus, using model-based rates at all ages would overestimate mortality and, thus, underestimate life expectancy. We opted to take a middle position: the use of proportional life expectancy (PLE).18,29 It can be shown that this method has implications for the EDR at every age,18,29 upon which it follows that our approach here could rely equally on the rates of Table 4 or the EDRs of Table 5. For females, the corresponding mortality rates are shown in Table 6, and the EDRs in Table 7.

Table 6

Mortality rates for otherwise healthy 65-year-old Caucasian females based on the models of Table 3

Table 7

Excess death rates for otherwise healthy 65-year-old Caucasian females, computed as Table 6 less the mortality rates for females aged 65 in the general population (0.0120)

Life expectancies based on the rates of Tables 4 and ​and55 are given in Table 8. As can be seen, the best group – never smokers with no significant lung disease and no medical conditions – have a life expectancy of 17.8 additional years. Not surprisingly, this is higher than the corresponding figure in the United States general population (16.8 years). By contrast, current smokers with no lung disease have a life expectancy of 14.3 years, or 3.5 years lower than 17.8, similar to the finding of Doll and colleagues.32 As expected, the presence of COPD further decreases the life expectancy.

Table 8

Life expectancies for otherwise healthy 65-year-old Caucasian males, based on the rates in Tables 4 and ​and5.5. See also Figure 6

Current smokers with stage 1 COPD have a life expectancy of 14.0 years, or 0.3 years lower. Smokers with stage 2 COPD have a life expectancy of 12.1 years, or 2.2 years lower. Those with stage 3 or 4 COPD have a life expectancy of 8.5 years, or 5.8 years lower. Former smokers lose 0.5 years for smoking, 1.4 additional years for stage 2 COPD and 5.6 additional years for stage 3 or 4 COPD, compared with otherwise similar persons who do not have lung disease. By contrast, never smokers lose only 0.7 years for stage 2 COPD and 1.3 years for stages 3 or 4 COPD. The two cases with an increase in life expectancy for COPD compared with no lung disease (stage 1 COPD in former and never smokers) are undoubtedly both due to the comparatively large standard errors (not shown) in the respective stage 1 parameter estimates of Table 3. The standard errors are much smaller for the other parameters. In sum, the years of life lost due to stages 2, 3, or 4 COPD is significant in current and former smokers, and modest in nonsmokers and those with stage 1 COPD.

Table 9 shows the corresponding values for females (using the mortality rates in Table 6 or the EDRs in Table 7). As with males, the reductions in life expectancy are significant for both smokers and those with stage 2, 3, or 4 COPD. For example, never smokers with stage 3 or 4 COPD lose 1.9 years of life, while smokers with stage 3 or 4 COPD lose 9.0 years, or 44% of the 20.3 years that obtains for a never smoker with no lung disease. The life expectancies in Tables 8 and ​and99 are shown graphically in Figures 6 and ​and77.

Male life expectancy at age 65, stratified by smoking status and severity of COPD (See Table 8).

Female life expectancy at age 65, stratified by smoking status and severity of COPD (See Table 9).

Table 9

Life expectancies for otherwise healthy 65-year-old Caucasian females, based on the rates in Tables 6 and ​and7.7. See also Figure 7

As noted, the models of Table 3 can be used to compute mortality rates, and thus life expectancies, for any combinations of the covariates. We could thus construct tables similar to Tables 8 and ​and99 for persons aged 55 or 75, or those with diabetes.

Tips for Staying Healthy With Mild/Early COPD

The approach to treatment of COPD will vary to some extent, based on what stage of COPD you are currently at. In this post, we’ll discuss some tips for people who are in the earliest stages of COPD on how to stay as healthy as possible.

COPD is a chronic inflammatory condition resulting in impaired functioning of your airways and lungs. Over time, it will get progressively worse, but this can take many years. You may be diagnosed at any of the 4 stages of the illness. Those who are diagnosed when still at the mild stage have the best chance of slowing the progression.

When you are classified as having “mild COPD,” your airways are starting to show some of the effects of the disease, but your symptoms are not severe yet. In fact, the reason COPD is often missed during this stage is because you might only notice these symptoms during periods of exercise or other strenuous activity:

  • Wheezing
  • Shortness of breath
  • Cough
  • Fatigue

You may not even have any prescribed treatment at this stage, since your symptoms are generally few and far between.

Prevention and lifestyle changes to stay healthy with early stage COPD

1. Quit smoking if you are a smoker

Quitting smoking is the cornerstone of treatment in people with any stage of COPD, but is especially important in those still at the mild stage. If you continue to smoke, knowing that you have COPD, then your condition can only get worse, in a hurry. But if you make the effort to stop smoking, the benefits will be immediate:

  • Your symptoms, if you have any, will lessen or disappear for now.
  • You will reduce or prevent any further damage to your lungs.
  • You will greatly slow down how fast your disease progresses and put off serious complications, such as death.

In short, you will feel better when you quit smoking. Talk with your doctor about the best way to quit. Some people prefer to quit cold turkey, while others will benefit from cutting down gradually, with the assistance of medication. There may also be support groups or special “quit smoking” programs available to help you.

2. If prescribed, use your short-acting bronchodilator

This is a type of inhaler, also called a rescue or quick-relief inhaler. The most common names of this type of medicine include Proventil and Albuterol.

This type of medicine does not cure or treat the COPD, nor does it prevent symptoms from occurring. But it will relieve symptoms should you have them. The inhaler expands and relaxes your airways and lungs for a period of time.

If your symptoms occur more frequently or are persistent despite using the rescue inhaler, talk with your doctor. It may be that you need to use the inhaler regularly, rather than just as needed. Or you may need to add a long-acting bronchodilator, an inhaled steroid or some other type of medication.

3. Avoid illness

Even with mild COPD, you are at an increased risk for respiratory infections. So, to stay healthy, you need to take steps to avoid being exposed to germs that cause this type of infection. Your first step is to get a yearly flu shot and a periodic pneumonia vaccine.

Also, do what you can to avoid coming into contact with others who are sick or who might be carriers of infection. During cold and flu season in the winter, it might be best to avoid being in public places as much as you can. In any event, practice thorough hand-washing when using public restrooms, etc.

4. Keep your heart healthy

In research called The Lung Health Study, experts found that heart disease was one of the most common causes of hospitalization in people with mild COPD. In fact, the risk of heart disease is doubled in people who have mild COPD, as compared to those who do not have COPD.

Researchers are not entirely sure why this is, but have suggested some of all of the following:

  • Chronic inflammation
  • Oxidative stress
  • Gene mutations
  • Shared risk factors

Research suggests that steroid therapy, either orally or via inhaler, may be useful in preventing heart disease in people with mild COPD, but this is not conclusive and more studies are needed. Meanwhile, you can help yourself by making healthy food choices and by staying as active as possible.

Eating right will help you feel better, give you more energy and may even boost your immune system. If you need to lose weight, eating healthy will also help with that, and that can help reduce your symptoms, such as shortness of breath during activity.

Being active can increase your muscle tone and endurance, improve your mood, help you stay independent and even improve your lung function. If you haven’t been active for some time, start slow and increase from there. Walking and swimming are often the easiest way to get started.

Do what you can to put these steps into action

People who have mild COPD don’t always find out in time to take the steps outlined above. But, if you have been diagnosed, then do what you can to put each of these tips into practice. I promise you that you will feel better if you do so.

Maintenance pharmacotherapy of mild and moderate COPD: What is the Evidence?

Chronic obstructive pulmonary disease (COPD) affects more than 24 million individuals in the United States, although at least half of the cases are not diagnosed. Proactive diagnosis and limitation of risk exposure from smoking or pollutants are important to improve prognosis. Pharmacologic treatments are prescribed according to COPD stage and symptoms. Mild COPD is symptomatically treated ’as needed’ with short-acting bronchodilators; major guidelines recommend starting maintenance treatment at the moderate COPD stage with long-acting bronchodilators; inhaled corticosteroids may be added for patients with more severe disease and frequent exacerbations. Maintenance therapy preserves 24-h airway patency, reduces exacerbations, and improves activity tolerance and health-related quality of life. Recent post-hoc analyses of large clinical trials that contain subgroups of patients with less severe COPD suggest that, similar to those with advanced disease, patients with moderate disease benefit from long-term maintenance therapies. Studies suggest symptomatic mild patients may also benefit. This concept needs to be prospectively tested in studies specific to these COPD disease stages. Proactive identification and pharmacologic intervention in early COPD has the potential to alter clinical outcomes throughout the disease course.

Stages of COPD: Mild through End-Stage COPD

What Happens in Severe Stage COPD?

Stage 3 or severe stage COPD has a large impact on people’s quality of life. Lung function continues to decline, and breathing becomes more difficult. Typically, COPD symptoms make it challenging to enjoy your favorite activities or to perform daily tasks. During this stage, many people feel more fatigue and have difficulty exercising.

Your doctor may prescribe corticosteroids to help reduce inflammation, combination inhalers and other kinds of medications or therapies.

What Happens in Very Severe or End-Stage COPD?

End-stage COPD or stage 4 is classified as very severe and often affects quality of life profoundly. Flare-ups and breathing issues may become life threatening. Your doctor may add to your existing COPD treatment plan or change it based on your needs.

By end-stage COPD, many people have trouble receiving enough oxygen. Low blood oxygen levels can lead to serious health conditions such as hypoxia or hypoxemia, cyanosis and other problems. When low blood oxygen levels occur, your doctor may prescribe oxygen therapy to help ensure your body receives adequate oxygen.

Taking Care of You and Your Lungs

Understanding the stages of COPD is one of the first steps you can take in becoming more proactive in your healthcare. As your COPD progresses, continue working with your doctor to modify your treatment plan as needed. Take note of any changes you notice in your symptoms, what triggers your symptoms to worsen and how COPD affects your ability to do daily activities. See your doctor immediately if you feel unwell or have changes in your health.

In combination with your current treatment plan, consider talking with your doctor about alternative therapies, such as lifestyle changes, herbs and supplements or cellular therapy. Interestingly, cellular therapy works to promote healing from within the lungs and may have the potential to improve breathing and quality of life. If you or a loved one has COPD, emphysema, chronic bronchitis or another chronic lung disease and would like to learn more about cellular therapy, contact us at 888-745-6697.

How Does COPD Progress?

Few things are as scary as the inability to breathe, one of the most serious symptoms of COPD progression.

“Initially, the patient will develop a cough and possibly sputum production,” says Brian W. Carlin, MD, an assistant professor of medicine at Drexel University School of Medicine in Philadelphia and the immediate past chairman of the COPD Alliance. COPD, or chronic obstructive pulmonary disease, affects your lungs and generally gets worse over time. As the elasticity in the airways and air sacs decreases, less air is able to go in and out as you breathe. Other complications of COPD — such as thickening or inflammation of the airways and more mucus accumulation — can further restrict airflow.

The progression of COPD can vary greatly. “COPD is an exaggeration of the natural aging process of the lung,” says Richard S. Novitch, MD, director of cardiopulmonary rehabilitation at Burke Rehabilitation Hospital in White Plains, N.Y. “Each individual is different, and the illness presents differently in them.”

How COPD Progresses

Think of COPD progression in stages. Stage I, or mild COPD, appears subtly — you might notice you feel short of breath when you exercise or do strenuous tasks around the house like yard work or carrying heavy objects. Sometimes an unexplained cough is the flashing red light. Many people at this stage don’t even realize they have a medical problem and fail to mention it to their doctors, instead chalking off the symptoms to age, weight gain, or smoking.

“While many smokers think that they have a ‘normal’ smoker’s cough, there is really no such thing as a ‘normal cough,’” says Dr. Carlin. “The cough often occurs years before the development of other symptoms, such as shortness of breath.”

Exacerbations are another warning sign of COPD, according to Carlin. Many people mistakenly believe these periods of increasing shortness of breath, cough, or sputum production are bronchitis, but in reality they are likely warning signs that the condition is progressing.

Moderate or stage II COPD is where most diagnoses are made. The symptoms at this stage of COPD will start to interfere with daily activities, making them harder to ignore.

Stage III or severe COPD is impossible to dismiss. “This is when patients are usually no longer able to work and have significant quality-of-life issues,” says Meg Schneider, co-author with Kevin Felner, MD, of COPD for Dummies. At stage III, you often feel short of breath even when sitting or lying down, Dr. Schneider explains. You cough frequently and often cough up a lot of mucus. Your immune system is weak, making you more susceptible to colds and other respiratory infections, and it takes much longer to recover. Fatigue, muscle weakness, and lack of appetite are also common.

Slowing the Progression of COPD

Smoking is the No. 1 risk factor for developing COPD and worsening of symptoms, so quitting is key in trying to slow the condition’s progression. “The sooner you quit, the sooner you stop the damage to your lungs,” says Schneider.

Lighting up is not the only cause, however. Exposure over a long period of time to dust, certain chemicals or fumes, secondhand smoke, and other air pollution can also contribute to COPD, so avoiding these situations is critical.

Getting the right treatment is important, too. With mild COPD, a fast-acting inhaler can help constricted airways on an as-needed basis. Longer-acting bronchodilators (which can keep airways open) or inhaled steroids may be prescribed for stage II COPD. Stage III requires intensive treatment usually including steroids, oxygen, bronchodilators, and sometimes even surgery. Pulmonary lung rehabilitation is another option to help you stay active. Your doctor is the starting point for any of these approaches.

Finally, positive lifestyle habits can help slow COPD progression and boost your overall health. These include regular exercise, a healthy diet in order to maintain an ideal weight, and getting enough rest.


There are two novel findings in this long term observational study of a large sample of COPD patients from the BODE cohort. First, that COPD is usually a non-progressive disease with less than 30% of the patients having a worsening of their GOLD spirometric grades of AL over at least 4 years of follow-up. Second, approximately 10% of the patients improved their spirometric values sufficiently to have an improvement in their GOLD spirometric grades of AL. These findings should contribute to challenge the current negative paradigm by providing a more positive perspective of a disease usually considered to be progressive.

Traditionally, and based primarily on the epidemiological observation from Fletcher and Peto , COPD has been viewed as a “usually progressive disease” where patients are diagnosed at less severe spirometric grades and then progress over time to more severe grades. . However, this concept has been recently challenged in several studies. Sanchez-Salcedo et al. demonstrated that the lung function decline profile is similar in young COPD patients and in those with older age, a finding that is not consistent with a progressive deterioration of lung function over time. More evidence suggesting that lung function progression in COPD is heterogeneous has been provided by three important studies . Casanova et al. followed 751 patients from the BODE database for a mean time of 5 years, and found that only 18% were “fast decliners” with a mean FEV1 decline of 86 ml/year. Similar results were reported by Nishimura et al. , who analyzed a smaller sample of 261 patients also followed for 5 years, reporting a similar proportion (25%) of “rapid decliners” who had a mean FEV1 decline of 61ml/year. Vestbo et al. , also reported the analysis of 2163 patients from the ECLIPSE study followed for 3 years, and observed that at least 38% of the patients had a yearly mean absolute FEV1 decline greater than 38ml/year. All of these studies concentrated primarily on the factors associated with a rapid decline in lung function, even though all of them noted the existence of a large group of patients who declined minimally and a small group that actually showed improvement in their lung function. These studies focused on the mean and individual yearly absolute FEV1 change in ml and did not relate the magnitude of the changes to shifts in GOLD spirometric AL grades, thereby limiting the clinical implications of the findings.

More recently, Casanova et al. explored the CHAIN COPD Spanish cohort and reported the one year longitudinal changes of GOLD spirometric grades of AL in this population . They noted that 72% of the patients remained in the same GOLD spirometric grade of AL and 13% actually improved, but the changes over that short period of time were not related to mortality or other outcomes. Agusti et al. in the ECLIPSE study also explored the longitudinal behavior of the GOLD spirometric grades of AL over 3 years but only analyzed the new ABCD GOLD classification and did not explore the relationship between those changes and outcomes.

The present study expands on these observations exploring the long term changes in GOLD grades in a large sample of well characterized COPD patients. It has the strength of including patients that were followed for at least 8 years (many up to 10–12 years). The purposeful inclusion of a second group of COPD patients who died after a minimum of 4 years of follow up, was designed to minimize the potential bias of including only survivors that would have a better course. The fact that the proportion of patients that improved the GOLD spirometric grade of AL was similar in survivors (with a longer follow up time) and non-survivors, and that the proportion of patients that remained stationary (62% and 65%) was also similar in both groups, would suggest that the improvement or stability observed is not spurious and is likely real.

The meaning of an improvement in GOLD spirometric grade has not been validated although several studies have consistently shown that the grades themselves are very good predictors of mortality . The actual reasons for this cannot be discerned in this study since it was not planned to explore any intervention other than optimal COPD care, but it does raise the possibility that the current standard of care is effective and provides strong support for a positive attitude towards patients with this disease, independent of the severity of the condition. In this regard, we observed no special characteristic that helped identify patients likely to improve over time, except for the fact that the baseline FEV1 was lower in those patients who had the most improvement. We have no explanation for this observation, except that the proportion of patients who quit smoking was higher, and the total amount of cigarettes smoked was lower, in patients who remained stable or improved compared with those that worsened, although it failed to reach statistical significance.

The present study has several limitations. Firstly, the findings presented are restricted to the type of patients included in this cohort: mainly male COPD patients attending pulmonary clinics. We do not know if women and/or patients attending primary care clinics will have the same behavior. Secondly, patients were managed differently over time as our capacity to treat them was influenced by the advent of newer therapies. This may have influenced the rate of FEV1 decline. However, this is true of all observational cohorts which by and large reflect real life medicine. On the other hand, the large number of patients and the international nature of the study decreases the chance that a systematic bias may have been applied to individual patients according to the GOLD spirometric grading. Our data (Table 2) shows that all groups had the same proportion of treatments regimens, suggesting that at least in this cohort treatment option had little effect on spirometric GOLD grading changes. We also acknowledge that we have no precise information on what happens in between the recorded visits and we only present a simple bivariate analysis, with all the potential limitations this could have. Thirdly, the BODE international cohort did not prospectively record the yearly exacerbation rate that could have had an impact on the progression of lung function, a weakness that may limit the strength of our findings. However, if we evaluate the results of the ECLIPSE study, where the exacerbation rate had little effect on FEV1 decline (only 2 ± 0.5ml/year for each exacerbation) the potential effect of this limitation is small . Lastly, we should not forget the potential role of the “size effect” on the change. We used a change of at least 1% to consider either an improvement or a deterioration, knowing that such a small change in lung function probably does not imply a clinically important difference. Acknowledging this important limitation, if we would have used a higher cut off threshold to consider a change, then a much smaller percentage of patients would have improved or deteriorated, giving further support to the main message of the present work that COPD is “mainly a non-progressive disease”.

In summary, the present study suggests that COPD is not markedly progressive in patients cared for in pulmonary clinics of tertiary university care centers, since a large proportion of patients attending clinics do not have changes, or actually improve, in their GOLD spirometric grades of AL. This finding changes the long-term perspective of the disease from a nihilistic one that limits the potential for improvement to a more positive one that can be used to motivate patients to adopt healthier lifestyles and remain adherent to their treatment.

COPD 101


  • Do not use ANORO to treat sudden symptoms of COPD. Always have a rescue inhaler with you to treat sudden symptoms.
  • Do not use ANORO if you have a severe allergy to milk proteins or are allergic to any of the ingredients in ANORO. Ask your healthcare provider if you are not sure.
  • Do not use ANORO if you have asthma.
  • Do not use ANORO more often than prescribed.
  • Do not take ANORO with other medicines that contain a long-acting beta2-adrenergic agonist (LABA) or an anticholinergic for any reason. Tell your healthcare provider about all your medical conditions and about all the medicines you take.
  • Call your healthcare provider or get medical care right away if your breathing problems get worse, if you need to use your rescue inhaler more often than usual, or if your rescue inhaler does not work as well to relieve your symptoms.
  • ANORO can cause serious side effects, including:
    • COPD symptoms that get worse over time. If this happens, do not increase your dose of ANORO; instead, call your healthcare provider.
    • symptoms of using too much of a LABA medicine, including:
      • chest pain
      • increased blood pressure
      • fast or irregular heartbeat
      • headache
      • tremor
      • nervousness
    • sudden breathing problems immediately after inhaling your medicine. If you experience this, stop using ANORO and call your healthcare provider right away.
    • serious allergic reactions. Call your healthcare provider or get emergency medical care if you get any of the following symptoms:
      • rash
      • swelling of your face, mouth, and tongue
      • hives
      • breathing problems
    • effects on heart.
      • increased blood pressure
      • chest pain
      • a fast or irregular heartbeat, awareness of heartbeat
    • effects on nervous system.
      • tremor
      • nervousness
    • new or worsened eye problems, including acute narrow-angle glaucoma that can cause permanent loss of vision if not treated. Symptoms may include:
      • eye pain or discomfort
      • nausea or vomiting
      • blurred vision
      • seeing halos or bright colors around lights
      • red eyes
        • If you have these symptoms, call your healthcare provider right away before taking another dose.
    • urinary retention. People who take ANORO may develop new or worse urinary retention. Symptoms may include:
      • difficulty urinating
      • painful urination
      • urinating frequently
      • urination in a weak stream or drips
        • If you have these symptoms, stop taking ANORO and call your healthcare provider right away before taking another dose.
    • changes in laboratory blood levels, including high levels of blood sugar and low levels of potassium.
  • Common side effects of ANORO include:
    • sore throat
    • sinus infection
    • lower respiratory infection
    • common cold symptoms
    • constipation
    • diarrhea
    • pain in your arms or legs
    • muscle spasms
    • neck pain
    • chest pain

American Journal of Respiratory and Critical Care Medicine

Discussion Section:

This observational study of patients with COPD attending pulmonary clinics has several important findings. First, only a small proportion of patients have statistically significant slope decline of the FEV1 over the time of the study. Second, a rapid progression of COPD as measured by increase in the BODE index with significant slope change also occurs in a small proportion of patients but the patients are different from those with accelerated lung function decline. Third, there are decliners with significant slope changes at all stages of GOLD obstruction. These results not only support the use of different variables to follow COPD progression but also suggest that disease “activity” and disease “severity” are different concepts and should be considered when assessing patients with COPD.

To our knowledge, this study represents the longest observational study in patients with COPD where other parameters different from the FEV1, such as the BODE index have been monitored. The most important contribution of this study is the individual longitudinal analysis of disease progression. Previous studies did not address individual patient variability because they evaluated FEV1 changes using mean group value (4–6). The rate of change in FEV1 is variable over time (Figure 2). The decrease of 28 ml/yr in the FEV1 in the nonsignificant slope decliner group is in agreement with the findings reported by Kohansal and coworkers (17) in the asymptomatic smoker group of the observational Framingham cohort study. However, we want to clarify that the inability to show a significant physiologic decline in a given subject does not necessarily mean that in that particular subject the underlying disease is not progressing; in addition, the inability to show a significant physiologic decline in a given subject could be influenced by other factors, such as variability in technique or environmental exposures and insufficient number of measurements independent of the course of the underlying lung pathology. However, in decliners with significant slope change, the FEV1 decline doubled the mean rate of decline reported in those who smoke in the study by Kohansal and coworkers (17) and that observed in the TORCH and UPLIFT trials (5, 6), likely because statistically and nonstatistically significant decliners contribute to the mean longitudinal values reported in these trials. Our results support the concept first discussed by Burrows (18), who pointed out that several “natural histories” are possible in patients with COPD and highlights the weakness of the “natural history” proposed by Fletcher and Peto (3). According to this model, one might expect patients with severe COPD to be older than patients with milder COPD. However, in our cohort the age was similar in all GOLD stages, a finding also observed by Agusti and coworkers (19) in the well-characterized COPD ECLIPSE cohort study. This observation could be explained by sampling bias related to subject recruitment into the BODE cohort, but it could also be that patients are already compromised at an earlier age and they are following parallel paths thus ending at different stages but at similar age. Independent of the reason, our results confirms the clinical observation that many patients with COPD maintain lung function independent of the stage at the time of diagnosis. No difference was observed in medication treatment between decliners with and without significant slope change and no difference was observed in the change of medication, which could indicate differential response to therapy among groups over time.

A very interesting finding in this study was the presence of decliners with significant slope changes at all GOLD stages. This suggests that some patients can move from a milder to a more severe stage but on average this takes 2 to 3 years to occur, as shown in Figure 3. In addition, the presence of decliners at all GOLD stages minimized the possibility that those patients with lower FEV1 at baseline had lost capacity to decline over time because of a ceiling effect. This finding supports the novel concept that disease severity (degree of impairment) should be distinguished from disease activity (rate of progression), and that thinking and research effort should be adjusted with this concept in mind. Moreover, this is consistent with a great individual variability over time suggesting that the disease progresses at different rates in different individuals (18).

Given the extensive characterization of the BODE cohort several factors thought to be involved in COPD progression can be evaluated. The analysis confirms previous studies that at baseline, a higher FEV1 and a lower BMI were associated with significant slope FEV1 decline (5). The most rapid FEV1 decline in patients with lower BMI suggests an association between systemic involvement and pulmonary disease progression in COPD. Previous studies have observed an inverse relationship between BMI and alveolar wall destruction (20). Currently, it is unclear if airway disease and emphysema have the same natural history (7). It is known that the presence of both lesions could vary greatly among different individuals. Nevertheless, a substantial difference in BMI in the decliner group was not observed.

Previous observations that smoking status affects the rate of FEV1 decline could not be confirmed. Tobacco smoking is the main risk factor for COPD, but previous studies have shown that the relationship between smoking exposure as gauged by self-reported cigarette use and airflow obstruction is poor (19). This could be related to an imprecise estimation of the cumulative exposure to tobacco smoke or a weaker association between pack-years and lung function, where a larger number of patients are needed. Although the Lung Health Study demonstrated a reduction in the rate of FEV1 decline with successful cessation among patients with mild disease (21), it is unknown whether this beneficial effect also occurs in severe disease (7). Recently, some authors have proposed that COPD progression may be the result of inflammatory or autoimmune processes that perpetuate in time in certain patients long after smoking cessation has occurred, thus erasing the association thought to exist between intensity of smoking and COPD (22, 23). In addition, other factors yet unexplored, such as different genetic susceptibility and environmental impact, may be important in the development and heterogeneous progression of COPD (2, 24, 25).

As was the case for smoking intensity and status, previous observations that exacerbations were associated with rapid rate of FEV1 decline could not be confirmed (5, 16). In those studies, however, the effect was modest and the difference in results may be explained by patient selection and the fact that we used individual slopes to determine each patient’s rate of decline compared with mean values in the other studies. However, our findings are not unique; indeed, in a recent large epidemiologic study there was no association between rapid lung function decline and COPD hospitalization (26). More studies in different settings are needed to evaluate the magnitude of the impact of exacerbations on FEV1 decline in patients with COPD.

Unique to this report is the analysis of the BODE index progression over time. Surprisingly, only 14% of patients had a statistical increase in BODE over the study period. However, there was very little concordance between lung function decline and BODE index increase, indicating that over time, changes in BODE values provide additional prognostic information. Indeed, only the BODE change in the patients with no change in FEV1 showed an independent association with increased risk of dying over the study period. There is very little information in COPD about the temporal behavior of other factors different from FEV1 (27, 28). Two previous studies have shown a decline of exercise capacity in patients with more severe airflow limitation. This has great relevance because at this level of disease severity, FEV1 behaves as a more rigid and less sensitive parameter to detect changes. The BODE index, which includes an exercise capacity evaluation, provides a better predictive prognostic tool in patients with COPD (10). Indeed, longitudinal changes in the BODE index with and without therapeutic interventions have been associated with quality of life and survival among stable patients with COPD (29–31). A physiologic or clinical parameter that predicted a rapid progression of BODE was not found. Further research in this area is important and the description of new biomarkers could help better discriminate these subgroups of patients. The low concordance between FEV1 and BODE index progression and the predictive capacity of BODE for mortality in the statistical decliners with significant slope change supports the need for a multidimensional severity assessment to better evaluate the COPD heterogeneity and complexity.

The present study has some limitations. First, few women were included, and the findings here reported cannot be extended to that sex. Although a recent clinical trial did not observe sex differences in FEV1 decline (5), further studies should be performed to evaluate this issue. The lack of more women in the study was not by design, because the opportunity to join the study was offered independent of sex. Second, there were important differences in the sample size in both participating centers. However and importantly, the percentage of patients with significant FEV1 decline was similar in both centers and reinforces the main findings. Third, the exact cause of death could not be thoroughly determined because there was no professional adjudicating committee. This has been a problem for all observational studies, unlike the large drug trials where the available resources have allowed for committees to be well chartered. However, cause of death was not the major reason for this study and has no impact on the conclusions. Fourth, there were a number of patients who only had two lung function measurements and were not included in the slope analysis. To build a solid mathematical slope we required at least three measurements over time. Because it was believe that this has more value, a larger dropout rate was accepted. However, if all 447 patients who were excluded from the analysis were assigned to the statistical decliners group, most patients (618 or 51%) would still have had no significant decline in the FEV1. Perhaps the number of decliners was underestimated because of the dropout rate, but we feel very confident that the findings are real. Finally, the BODE cohort is obtained from an observational study of patients attending pulmonary clinics and is not a general medical practice or population-based study. Hence, a potential sampling bias cannot be excluded and the findings may not be generalizable to all COPD populations. A small proportion of patients with stage I was included. However, a sufficient and proportional sample of patients in the other stages was included and the stratified analysis supports the main results.

In summary, this longitudinal observational study highlights the heterogeneity of the current natural history of COPD. The findings address questions left unanswered by the Fletcher-Peto curve. Importantly, for the first time the heterogeneous progression of FEV1 and the BODE index are described and it was shown that most patients had no change over a prolonged period of observation. It is also concluded that the progression of COPD differs depending on the variable used to characterize it, and the limitations of FEV1 alone in the understanding and monitoring of this disease are confirmed.

Whilst there is currently no cure for Chronic Obstructive Pulmonary Disease (COPD), evidence shows that early diagnosis, combined with disease management programs, can reduce the impact COPD, improve quality of life, slow disease progression, reduce mortality and keep you out of hospital. Here are some tips to slow the progression of your COPD.

Stop smoking

If you smoke, quitting is the single most important thing you can do to improve your health, lung function and slow the progression of your COPD. If you continue to smoke, this will affect your health and respiratory symptoms, so the sooner you quit, the better your chances of living well with COPD. A quit plan can help you reflect on why you smoke, your motivations for quitting and help you choose your preferred quit tools.

Keep active with exercise

Research shows that regular exercise can help maintain your fitness and wellbeing, as well as reduce symptoms of breathlessness, making everyday activities easier.

Attend pulmonary rehabilitation

Pulmonary rehabilitation is an exercise and education program provided by specially trained health professionals which teaches you how to exercise safely and how to manage your breathlessness. Research shows that pulmonary rehabilitation is one of the best things you can do to improve symptoms and quality of life.

Lungs in Action

After you finish pulmonary rehabilitation, it is important to continue exercising to help maintain your physical fitness and lung health. Lung Foundation Australia’s Lungs in Action program is a safe and fun community-based exercise class designed to help people with a chronic lung disease maintain the benefits achieved through pulmonary rehabilitation.

Get your vaccinations

Protect yourself from influenza and pneumonia by making sure your vaccinations are up-to-date.

Maintain a healthy lifestyle

Keeping within a healthy weight range is important if you have COPD. Eating a balanced diet, maintaining a healthy weight and getting plenty of rest will help to ensure you are healthy and have enough energy to enjoy life.

Take your medicine as instructed

It is essential that you take your medicines as instructed by your doctor, even when you feel well – they can help prevent your COPD symptoms from getting worse in the long-term. Do not be tempted to decide when and how much medicine you will take, as this may result in you not getting the most benefit from your medicine.

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