Correspondence

Change in FEV₁ over Time in COPD

N Engl J Med 2011; 365:2540-2541December 29, 2011

Article

To the Editor:

Vestbo and colleagues (Sept. 29 issue)1 reported on the variability in the rate of the decline in forced expiratory volume in 1 second (FEV₁) in patients with chronic obstructive pulmonary disease (COPD) from the cohort in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study (ECLIPSE) (ClinicalTrials.gov number, NCT00292552) and stress the importance of smoking cessation to attenuate this decline. Although large drug trials have provided evidence for some attenuation of lung-function decline,2,3 we do not agree with the authors' interpretation that intensive pharmacologic treatment resulted in the rather mild decline seen in the ECLIPSE cohort. Although the mild — or even reversed — decline could be due to regression to the mean in these patients with relatively severe COPD (i.e., the mean FEV₁ was 48% of predicted), we think it reflects the 64% of participants who did not smoke or did not continue to smoke. Since smoking is known to be the main determinant of a decline in lung function, and smoking cessation is by far the most effective intervention to prevent both the development and the progression of COPD,3-5 the distribution of the rate of decline within the subgroups of smokers and nonsmokers would be of interest.

Wouter D. van Dijk, M.D.
Tjard R. Schermer, Ph.D.
Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
w.vandijk@aios.umcn.nl

No potential conflict of interest relevant to this letter was reported.

5 References

1. 1

   Vestbo J, Edwards LD, Scanlon PD, et al. Changes in forced expiratory volume in 1 second over time in COPD. N Engl J Med 2011;365:1184-1192
   Full Text | Web of Science | Medline

2. 2

   Tashkin DP, Celli B, Senn S, et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 2008;359:1543-1554
   Full Text | Web of Science | Medline

3. 3

   Celli BR, Thomas NE, Anderson JA, et al. Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study. Am J Respir Crit Care Med 2008;178:332-338
   CrossRef | Web of Science | Medline

4. 4

   Anthonisen NR, Connett JE, Kiley JP, et al. Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. JAMA 1994;272:1497-1505
   CrossRef | Web of Science | Medline

5. 5

   Kuller LH, Ockene JK, Meilahn E, Wentworth DN, Svendsen KH, Neaton JD. Cigarette smoking and mortality. Prev Med 1991;20:638-654
   CrossRef | Web of Science | Medline

To the Editor:

Vestbo et al. found a mean decline in FEV₁ of 33±2 ml per year in patients with COPD, which is substantially less than the 64 ml per year observed by Fletcher and Peto in 1977.1 We would like information about the effect on the decline in the ECLIPSE cohort of pulmonary rehabilitation, which is recognized as an effective treatment for COPD.2 Some studies report that the decline in FEV₁ in patients with COPD who undergo such rehabilitation is significantly lower than that achieved with standard drug treatment.3,4

Gian Galeazzo Riario Sforza, M.D.
Cristoforo Incorvaia, M.D.
Istituti Clinici di Perfezionamento, Milan, Italy
griariosforza@icp.mi.it

No potential conflict of interest relevant to this letter was reported.

4 References

1. 1

   Fletcher C, Peto R. The natural history of chronic airflow obstruction. Br Med J 1977;1:1645-1648
   CrossRef | Web of Science | Medline

2. 2

   Nici L, Donner C, Wouters E, et al. American Thoracic Society/European Respiratory Society statement on pulmonary rehabilitation. Am J Respir Crit Care Med 2006;173:1390-1413
   CrossRef | Web of Science | Medline

3. 3

   Cote CG, Celli BR. Pulmonary rehabilitation and the BODE index in COPD. Eur Respir J 2005;26:630-636
   CrossRef | Web of Science | Medline

4. 4

   Stav D, Raz M, Shpirer I. Three years of pulmonary rehabilitation inhibit the decline in airflow obstruction, improves exercise endurance time, and body-mass index, in chronic obstructive pulmonary disease. BMC Pulm Med 2009;9:26-30
   CrossRef | Medline

Author/Editor Response

In their attempt to understand the reason for the lower-than-expected decline in FEV₁, van Dijk and Schermer think it unlikely that drug treatment is an acceptable explanation. We concur, since such statements cannot be made based on observational data — as we explained in our article. Nevertheless, since most patients were cared for in specialist settings, our findings may not be valid for patients with COPD who were followed and managed differently. We agree that smoking cessation is essential. Our analyses showed that FEV₁ declined more rapidly among current smokers than among former smokers (21±4 ml per year, P<0.001); however, there is substantial overlap between these two groups in terms of the distribution of the rate of this change. We believe that the linear decline over 3 years argues against a strong effect of regression toward the mean. Had there been a strong effect, it would have most strongly affected the first measurements, thus leading to nonlinear changes over time. We maintain that a revision of the general understanding of the natural history of COPD is needed in light of our findings and of those reported from other observational studies in COPD.1,2

Riario Sforza and Incorvaia wonder whether pulmonary rehabilitation could have influenced the decline in FEV₁. We are unable to comment on this issue, since we have no detailed information on such rehabilitation before the patients entered the study or during follow-up. However, even if we had such data, the biases related to studying the effects of interventions in observational cohort studies would be as relevant for pulmonary rehabilitation as for pharmacologic treatment.

Jørgen Vestbo, Dr.Med.Sc.
Hvidovre Hospital, Hvidovre, Denmark
jvestbo@dadlnet.dk

for the ECLIPSE Study Investigators

Since publication of his article, the author reports no further potential conflict of interest.

2 References

1. 1

   Casanova C, de Torres JP, Aguirre-Jaíme A, et al. The progression of chronic obstructive pulmonary disease is heterogeneous: the experience of the BODE cohort. Am J Respir Crit Care Med 2011 August 11 (Epub ahead of print).
   

2. 2

   Nishimura M, Makita H, Nagai K, et al. Annual change in pulmonary function and clinical phenotype in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2011 October 20 (Epub ahead of print).