Day and Night Control of COPD and Role of Pharmacotherapy: A Review

Figures & data

Figure 1 Circadian variation of COPD symptoms: *p<0.001 versus “midday”, “afternoon”, “evening”, “night” and “difficult to say” groups; p=0.006 versus “no particular time of day” (all COPD patients); ^†p<0.001 versus “midday”. Patient insight into the impact of chronic obstructive pulmonary disease in the morning: an internet survey. Partridge MR, Karlsson N, Small IR, et al. Curr Med Res Opin. 2009;25:2043–2048. Informa UK Ltd, trading as Taylor & Francis Group, reprinted by permission of the publisher (Taylor & Francis Ltd, http://www.tandfonline.com).⁴

Figure 2 COPD pathophysiology in determining nocturnal symptom variability.

Table 1 Tools to Assess COPD Symptoms Referring to Daily Variability

Questionnaires or Patient Reported Outcomes	Instrumental Tools
CAT^Citation43	Plethysmography (FEV1, FEV1/FVC, IC/TLC, FRC, RV)
CDLM^Citation42	6MWT
mMRC	Pulse oximetry
E-RS^Citation44,Citation45	Cardio-respiratory tools (LEOSound)
MCC^Citation46	Polysomnography
CASIS^Citation53
JSEQ
GCSQ^Citation42
NiSCI
EMSCI
MEMSI
Night-time, morning and daytime COPD symptoms

Abbreviations: CASIS, COPD and Asthma Sleep Impact Scale; CAT, COPD Assessment Test; CDLM, capacity of daily living during the morning; EMSCI, early morning symptoms of COPD instrument; GCSQ, Global Chest Symptoms Questionnaire; JSEQ, Jenkins Sleep Evaluation Questionnaire; mMRC, modified Medical Research Council; E-RS, Evaluating respiratory symptoms; MCC, modified control criteria; MEMSI, Manchester Early Morning Symptoms Index; NiSCI, Night-time Symptoms of COPD Instrument; 6MWT, 6-minute walking test.

Table 2 Charactestistics of the Main Trial Reported by the Board

Trial	Drugs	Population	Primary Outcome	Results	Outcomes Related to Symptoms Control
WISDOM^Citation76	Tiotropium (18 μg once daily), salmeterol (50 μg twice-daily), and fluticasone propionate (500 μg twice-daily) vs tiotropium-salmeterol	2485 patients with a history of exacerbation of COPD	Time to the first moderate or severe COPD exacerbation; change in trough FEV1	Noninferiority; reduction in FEV1 in the second group	SGRQ, mMRC
SUNSET^Citation79	Indacaterol/glycopyrronium (110/50 μg once-daily) vs tiotropium [18 μg] once-daily + salmeterol/fluticasone propionate [50/500 μg] twice-daily)	1053 nonfrequently exacerbating patients with moderate-to-severe COPD	Change from baseline in trough FEV1; moderate or severe exacerbations	Reduced FEV1 in the first group; no difference in exacerbations	TDI, SGRQ, mean rescue medication use
TRIBUTE^Citation74	Two inhalations of extrafine beclometasone dipropionate, formoterol fumarate, and glycopyrronium (87 μg/5 μg/9 μg) twice-daily or one inhalation of indacaterol plus glycopyrronium (85 μg/43 μg) once-daily	1532 patients with severe or very severe COPD and at least one moderate or severe exacerbation in the previous year	Rate of moderate-to-severe COPD exacerbations across 52 weeks of treatment	Rate ratio of 0.848 (0.723–0.995, p=0.043) in favour f beclometasone dipropionate, formoterol fumarate, and glycopyrronium	SGRQ, SGRQ response (decrease from baseline in total score ≥4), rescue medication use, E-RS, CAT
IMPACT^Citation75	Once-daily combination of fluticasone furoate (100 μg), umeclidinium (62.5 μg) and vilanterol (25 μg) vs fluticasone furoate (100 μg) and vilanterol (25 μg), vs umeclidinium (62.5 μg) and vilanterol (25 μg)	10,355 COPD patients	Annual rate of moderate or severe COPD exacerbations	Fewer exacerbations in the triple therapy group than fluticasone furoate-vilanterol (rate ratio 0.85; 0.80–0.90; P<0.001) and than umeclidinium-vilanterol (rate ratio 0.75; 0.70–0.81; P<0.001)	SGRQ, health-related quality of life, BDI, TDI
KRONOS^Citation90	Budesonide/glycopyrrolate/formoterol fumarate metered-dose inhaler (320 μg/18 μg/9.6 μg) vs glycopyrrolate/ formoterol fumarate metered-dose inhaler (18 μg/9.6 μg) vs budesonide/formoterol fumarate metered-dose inhaler (320 μg/9.6 μg) vs open-label budesonide/formoterol fumarate dry-powder inhaler (400 μg/12 μg)	1902 COPD patients	FEV1 area under the curve from 0–4 h over 24 weeks, change from baseline in morning pre-dose trough FEV1	Improvement in FEV1 and in pre-dose trough FEV1 with the triple therapy	TDI focal score, change from baseline in daily rescue medication use, change from baseline in SGRQ total score, E-RS

Abbreviations: BDI, Baseline Dyspnea Index; CAT, COPD Assessment Test; mMRC, modified Medical Research Council; SGRQ, St. George’s Respiratory Questionnaire; TDI, Transition Dyspnea Index.

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