Modifying the Course of Chronic Obstructive Pulmonary Disease: Looking Beyond the FEV₁

Figures & data

Table 1.  GOLD spirometric classification of COPD according to FEV1.2

Stage	Definition
GOLD I	FEV1/FVC < 0.70; FEV1 ≥ 80% predicted
GOLD II	FEV1/FVC < 0.70; 50% ≤ FEV1 < 80%
GOLD III	FEV1/FVC < 0.70; 30% ≤ FEV1 < 50%
GOLD IV	FEV1/FVC < 0.70; FEV1 < 30%

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 sec; FVC, forced vital capacity; GOLD, Global Initiative for Obstructive Lung Disease.

Table 2.  Systemic manifestations and common co-morbidities in COPD (34).

Peripheral muscle deconditioning

Peripheral muscle wasting

Steroid myopathy

Anxiety, depression

Pulmonary hypertension, cor pulmonale

Osteoporosis

Coronary artery disease

Peripheral vascular disease

Stroke

Congestive heart failure

Normocytic anemia

Diabetes

Metabolic syndrome

Lung cancer

Pneumonia

Obstructive sleep apnea

Abbreviation: COPD, chronic obstructive pulmonary disease.

Figure 1.  Progression of airflow limitation in COPD (4). Abbreviations: COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 sec. Reproduced from Fletcher C, Peto R. The natural history of chronic airflow obstruction. Br Med J 1977 Jun 25; 1(6077)1645–1648, with permission from BMJ Publishing Group Ltd.

Figure 2.  Severity staging and natural history of COPD.44 Grouping by FEV1 would put together patient A (40 years old with a rapid rate of decline) and patient B (70 years old with a slower rate of decline). Conversely, patients of different ages with rapid disease progression (patients A and C) may have more features in common than patients with the same FEV1 percent of predicted and different rates of progression. Abbreviations: COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 sec; GOLD, Global Initiative for Obstructive Lung Disease. Reprinted from Rennard SI, Vestbo J. Natural histories of chronic obstructive pulmonary disease. Proc Am Thorac Soc 2008 Dec 15; 5(9):878–883, with permission of the American Thoracic Society. Copyright © 2012 American Thoracic Society. An official publication of the American Thoracic Society.

Figure 3.  An example of a rate-altering disease modification: smoking cessation. In the Lung Health Study (49), sustained quitters had a reduced rate of the loss of lung function in comparison to intermittent quitters. Reprinted from Anthonisen NR, Connett JE, Murray RP. Smoking and lung function of Lung Health Study participants after 11 years. Am J Respir Crit Care Med 2002 Sep 1; 166(5):675–679, with permission of the American Thoracic Society. Copyright © 2012 American Thoracic Society. Official Journal of the American Thoracic Society.

Figure 4.  Examples of status-altering disease-modifying therapies. Lung function in the TORCH50 (a) and UPLIFT51 (b) studies. Abbreviation: FEV1, forced expiratory volume in 1 sec. Reproduced by permission from (a) Calverley et al. (50) and (b) Tashkin et al. (51). Copyright © 2010 Massachusetts Medical Society. All rights reserved.

Table 3.  How good are we at modifying COPD?

	Lung Function		HRQL		Exacerbation		Exercise		Activity		Dyspnea		Mortality
Smoking cessation	Anthonisen^49	Y											Anthonisen^36	Y
	Godtfredsen^53	Y											Godtfredsen^53	Y
LABA	TORCH^50	Y	TRISTAN^54	N	TRISTAN^54	Y					TRISTAN^54 (SGRQ breathlessness)	Y	TORCH^50	N
	TRISTAN^54	*			TORCH^50	Y
	Van Noord^55	Y
	SUN/SHINE^56, 57	Y						.
TIO	UPLIFT^51	Y	UPLIFT^51	Y	UPLIFT^51	Y	Casaburi^61	Y			Casaburi (TDI)^58	Y	UPLIFT^51	Y
	Van Noord^55	Y	Casaburi^58	Y	Casaburi^58	Y	Maltais^62	Y
	Casaburi^58	Y	Tonnel^59	Y	Niewoehner^60	Y
LABA + ICS	TRISTAN^54	Y	TRISTAN^54	Y	TRISTAN^54	Y					TRISTAN^54 (SGRQ breathless-ness)	Y	TORCH^50	N
	TORCH^50	Y	TORCH^50	Y	TORCH^50	Y
	SUN/SHINE^56, 57	Y	ISOLDE^63	Y	SUN^56	Y
ICS	LHS^64	N	LHS^64	N	Vestbo^66	N					LHS (ATS)^64	Y	LHS^64	N
	TRISTAN^54	Y	TRISTAN^54	N	TRISTAN^54	Y					Vestbo (MRC)^66	N	TORCH^50	N
	TORCH^50	Y	ISOLDE^63	Y	ISOLDE^63	Y					TRISTAN (SGRQ breathless-ness)^54	Y
	ISOLDE^63	Y			TORCH^50	Y
	EUROSCOP^65	Y
	Vestbo^66	N
Oxygen							Emtner^67	Y	Lacasse^68	N			MRCWP^69 (men only)	Y
													NOTTG^70 (contin. O2)	Y
LVRS			Fishman^52	Y			Fishman ^52	Y					Benzo^71
			Benzo^71	Y									Fishman ^52	Y N
Pulmon. Rehab.							Casaburi^61		Pitta^74	Y			Puhan^73	Y
							Steele^72	Y	Sewell^75	Y
							Puhan^73	N	Steele^72	N
							Griffiths^47	Y	Walker^76	Y
								Y	Garcia-Aymerich^77	Y

This table summarizes statistically significant changes with different interventions versus placebo in the various COPD outcome domains discussed in the text.Y = treatment has demonstrated a statistically significant effect on outcome (irrespective of effect size). N = treatment has not demonstrated a statistically significant effect on outcome.

*TRISTAN results on lung function are not comparable to those of other studies because the main lung function measurement was a pre-study drug measurement at 12 hours after the last drug inhalation and post-values were post-salbutamol in all groups (including placebo group).

Abbreviations: COPD, chronic obstructive pulmonary disease; HRQL, health-related quality of life; ICS, inhaled corticosteroid; LABA, long-acting β-agonist; LHS, Lung Health Study; LVRS, lung volume reduction surgery; MRCWP, Medical Research Council Working Party; NOTTG, Nocturnal Oxygen Therapy Trial Group; SGRQ, St. George's Respiratory Questionnaire; TIO, tiotropium.