Exacerbation rate, health status and mortality in COPD – a review of potential interventions

Figures & data

Table 1 Comparison of 9 studies of exacerbations over 30 years

Author/Year	Country	N	Years	Patient type	Exac. freq	Follow up
Monto^Citation43	USA	142	1	COPD and NOCB^a	2.33	Telephone weekly
Fletcher^Citation17	England	792	8	Unselectedb	2.34	6 monthly
Kanner^Citation44	USA	84	4	Mixedc	0.34	Telephone Weekly
Anthonisen^Citation45	Canada	173	3.5	COPD	1.30	3 monthly
Seemungal^Citation48	UK	70	1.0	COPD	3.00	Diary cards
Seemungal^Citation46	UK	101	2.5	COPD	2.50	Diary cards
TORCH^Citation104	World wide	6112	3	COPD	1.13χ	3 monthly
INSPIRE^Citation51	Europe	1323	2	COPD	1.30δ	Diary cards
UPLIFT^Citation136	World wide	5993	4	COPD	0.85χ	3 monthly

Notes: ^aNOCB, Nonobstructed chronic bronchitis;

^b Included normal subjects;

^c Mixed, COPD and other airway diseases;

^χ Placebo group only;

^δ Mean value for both arms using the health care utilization definition. Using the symptom-based definition the mean number of exacerbations was approximately 3.00.

Figure 1 The interaction of safety, tolerability and efficacy.

Table 2 Safety and tolerability

Intervention	Safety	Tolerability	Remarks	Reference
ICS vs LABA vs Both vs Placebo	Significant increase in risk of ‘pneumonia’ in patients taking an ICS containing preparation (19.6% both, 18.3% ICS vs 12.3% placebo p < 0.001 or 13.3% LABA). ICS also associated with oropharyngeal candidiasis. No apparent effect of ICS on BMD or fracture risk, or of LABA on cardiovascular events.	Placebo: 44% withdrawal. RR in following groups compared to placebo 0.69 (0.62–0.78, p < 0.001) for both, 0.78 (0.70–0.86, p < 0.001) for LABA and 0.81 (0.72–0.90, p < 0.001) for ICS.	3 year study, 6184 in safety analysis	TORCH
ICS + LABA vs Tiotropium	Lower mortality in SFC vs TIO (3% vs 6%, p = 0.032) which may relate to more cardiovascular events in TIO. Increased pneumonia in SFC vs TIO (8% vs 4%).	ICS + LABA withdrawal 35% vs tiotropium 42% p = 0.005.	2 year study, 1323 patients randomized	INSPIRE
Tiotropium	All cause mortality vs placebo: OR 0.96, 95% CI 0.63–1.47. Compared with placebo greater dry mouth but not constipation, urinary retention or vascular/arrhythmias.		8002 patients	Barr^Citation186 Meta-analysis
ICS	Increased oropharyngeal candidiasis RR 2.1, 95% CI 1.53–3.10; bruising RR = 2.1; 95% CI 1.6–2.8 and lower mean cortisol. No mortality effect. Effect on BMD variable. No differences in cataract or fracture (but short follow up).		9 trials, 3976 patients	Alsaeedi^Citation188 Systematic analysis
LABA	No increased adverse events, clinical, laboratory or ECG, compared to placebo over 12 weeks.		135 salmeterol, 143 placebo.	Mahler^Citation116

Abbreviations: ICS, inhaled corticosteroids; LABA, long-acting β₂-agonists; BMD, bone mineral density; RR, relative risk; SFC, salmeterol fluticasone; TIO, tiotropium; OR, odds ratio; CI, confidence interval.

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