Frequent Chronic Obstructive Pulmonary Disease Exacerbators: How Much Real, How Much Fictitious?

Figures & data

Table 1.  Impact of frequent exacerbations on health related quality of life, using the St George's Respiratory Questionnaire (SGRQ)

	Number of patients	Study design	Duration (years)	Threshold for frequent exacerbations (n exacerbations per year)	Impact of frequent exacerbations on HRQoL (differences between frequent and infrequent exacerbations, expressed as score units)
					Baseline	End of study
Seemungal et al., 1998 (2)	70	Observational	1	≥3.0	NR	+15.1
Miravitlles et al., 2004 (3)	336	Observational	2	≥3.0	+7.2	+9.3
Soler et al., 2004 (4)	64	Case–control	1	≥3.0	+16.4	NR
Spencer et al., 2004 (5)	613	RCT	3	>1.65	+4.0	NR
Bourbeau et al., 2007 (6)	336	Observational	0.5	≥2.0	+4.0	+12.0

NC, no change compared to baseline; NR, not reported; RCT, randomized controlled trial.

Table 2.  Impact of frequent exacerbators on FEV₁ decline

	Number of patients	Study design	Duration (in years)	Frequent exacerbator definition (n of exacerbations per year)	Rate of accelerated FEV1 decline
					Infrequent exacerbations	Frequent exacerbations	p values
Kanner et al., 2001 (7)	5,887	Epidemiologic	5	≥1.50	Smoking status:	Smoking status:
					Sustained quitter: −13.0 mL yr^−1	Sustained quitter: −12.0 mL yr^−1.	NS
					Intermittent quitter: −32.6 mL yr^−1	Intermittent quitter: −52.0 mL yr^−1	<.05
					Continuous smoker: −55.4 mL yr^−1	Continued smoker: −69.4 mL yr^−1	<.001
Donaldson et al., 2002 (8)	32	Observational	4	≥2.92	−32.1 mL yr^−1	−40.1 mL yr^−1	<.05
Miravitlles et al., 2004 (3)	336	Observational	2	≥3.0	NR	NR	NS
Spencer et al., 2004 (5)	613	RCT	3	>1.65	−55 mL yr ^−1	−54 mL yr ^−1	NS
Cote et al., 2007 (15)	205	Observational	2	>2.0	NC	−4.0 (% predicted)	NS
Makris et al., 2007 (16)	102	Observational	3	>2.85	Smoking status:	Smoking status:
					Ex-smokers: −0.85 (% predicted)	Ex-smokers: −2.80 (% predicted)	= .017
					Smokers: −3.15 (% predicted)	Smokers: −4.10 (% predicted)

For abbreviations, see Table 1.

Figure 1.  Schemes of different terms related to COPD exacerbation. In (a) (“usual pattern”), symptoms increase beyond the usual daily variation and can decrease with or without treatment to complete recovery; in (b) (“treatment failure”), symptoms worsen during the exacerbation event such that further treatment is deemed; in (c) (“recurrence”), a new episode follows an earlier exacerbation with an interim period (namely, more than 4 weeks) of usually relatively good health status.

Table 3.  Risk factors

Older age (2, 4, 12)

Severity of COPD:

Increased baseline dyspnea (4, 12)

Low FEV1 (8, 10–12, 16, 41)

Low PaO2 (4, 12)

Frequent past exacerbations (2, 6, 42–44)

Chronic bronchial mucus hypersecretion (51)

Inflammation:

Higher airway inflammation (8, 45)

Higher systemic inflammation (46, 50)

Bacterial load (stable phase) (45)

Comorbidities/systemic manifestations:

Cardiovascular (4, 44)

Anxiety and depression (24)

Myopathy (26)

Seemungal TAR, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998; 157:1418–1422.

 PubMed Web of Science ®Google Scholar

Miravitlles M, Ferrer M, Pont A, Zalacain R, Alvarez-Sala JL, Masa F, Verea H, Murio C, Ros F, Vidal R; IMPAC Study Group. Effect of exacerbations on quality of life in patients with chronic obstructive pulmonary disease: a 2 years follow-up study. Thorax 2004; 59:387–395.

 Google Scholar

Soler JJ, Sánchez L, Román P, Martínez MA, Perpiña M. Risk factors of emergency care and admissions in COPD patients with high consumption of health resources. Respir Med 2004; 98:318–329.

 PubMed Web of Science ®Google Scholar

Spencer S, Calverley PMA, Burge PS, Jones PW. Impact of preventing exacerbations on deterioration of health status in COPD. Eur Respir J 2004; 23:698–702.

 PubMed Web of Science ®Google Scholar

Bourbeau J, Ford G, Zackon H, Pinsky N, Lee J, Ruberto G. Impact on patients’ health status following early identification of a COPD exacerbation. Eur Respir J 2007; 30:907–913.

 PubMed Web of Science ®Google Scholar

Kanner RE, Anthonisen NR, Connett JE. Lower respiratory illnesses promote FEV(1) decline in current smokers but not ex-smokers with mild chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001; 164:358–364.

 PubMed Web of Science ®Google Scholar

Donaldson GC, Seemungal TAR, Bhowmik A, Wedzicha JA. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 2002; 57:847–852.

 PubMed Web of Science ®Google Scholar

Cote CG, Dordelly LJ, Celli BR. Impact of COPD exacerbations on patient-centered outcomes. Chest 2007; 131:696–704.

 PubMed Web of Science ®Google Scholar

Makris D, Moschandreas J, Damianaki A, Ntaoukakis E, Siafakas NM, Milic Emili J, Tzanakis N. Exacerbations and lung function decline in COPD: new insights in current and ex-smokers. Respir Med 2007; 101:1305–1312.

 PubMed Web of Science ®Google Scholar

Soler JJ, Sánchez L, Latorre M, Alamar J, Román P, Perpiña M. The impact of COPD on hospital resources: the specific burden of COPD patients with high rates of hospitalization. Arch Bronconeumol 2001; 37:375–381.

 PubMed Web of Science ®Google Scholar

Paggiaro PL, Dahle R, Bakran I, Frith L, Hollingwoth K, Efthimiou J. Multicentre randomised in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. BMJ 2000; 20:1297–1303.

 Google Scholar

Burgel PR, Nesme-Meyer P, Chanez P, Caillaud D, Carré P, Perez T, Roche N. Cough and sputum production are associated with frequent exacerbations and hospitalizations in COPD subjects. Chest 2009; 135:975–982.

 PubMed Web of Science ®Google Scholar

Bhowmik A, Seemungal TAR, Sapsford RJ, Wedzicha JA. Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations. Thorax 2000; 55:114–120.

 PubMed Web of Science ®Google Scholar

Patel IS, Seemungal TAR, Wiks M, Lloyd-Owen SJ, Donaldson GC, Wedzicha JA. Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations. Thorax 2002; 57:759–764.

 PubMed Web of Science ®Google Scholar

Donaldson GC, Seemungal TAR, Patel IS, Lloyd-Owen SS, Bhowmik A, Wilkinson TMA, Maccallum PK, Wedzicha JA. Airway and systemic inflammation and decline in lung function, in chronic obstructive pulmonary disease. Chest 2005; 128:1995–2004.

 PubMed Web of Science ®Google Scholar

Niewoehner DE, Lokhnygina Y, Rice K, Kuschner WG, Sharafkhaneh A, Sarosi GA, Krumpe P, Pieper K, Kesten S. Risk indexes for exacerbations and hospitalizations due to COPD. Chest 2007; 131:20–28.

 PubMed Web of Science ®Google Scholar

Quint JK, Baghai-Ravary R, Donaldson GZ, Wedzicha JA. Relationship between depression and exacerbations in COPD. Eur Respir J 2008; 32:53–60.

 PubMed Web of Science ®Google Scholar

Decramer M, Gosselink R, Troosters T, Verschueren M, Evers G. Muscle weakness is related to utilization of health care resources in COPD patients. Eur Respir J 1997; 10:417–423.

 PubMed Web of Science ®Google Scholar