Figures
- Figure 1.
Prevalence (per cent and 95% confidence interval) of night-time symptoms among patients with chronic obstructive pulmonary disease aged >40 yrs with a history of smoking, stratified by forced expiratory volume in 1 s (FEV1) % predicted. Data are taken from [32].
- Figure 3.
Severity and impact of night-time symptoms among patients with chronic obstructive pulmonary disease treated with aclidinium bromide or placebo. The frequency of each variable was scored as follows: 0, never; 1, 1–2 times; 2, 3–4 times; 3, 5–6 times; and 4, ≥7 times. Weekly averages were analysed. *: p<0.05; **: p<0.01; ***: p<0.001 versus placebo. Reproduced from [77] with permission from the publisher.
- Figure 4.
Outcomes (survival and exacerbation frequency) among patients with overlap syndrome treated with continuous positive airway pressure (CPAP). COPD: chronic obstructive pulmonary disease. Reproduced from [89] with permission from the publisher.
Tables
- Table 1. Epidemiological studies of sleep disturbance and night-time symptoms in chronic obstructive pulmonary disease (COPD)
Citation Population/method Relevant results Klink and Quan [22] (1987) Prospective epidemiological study of 2187 adults
A diagnosis of “obstructive airways disease” identified by questionnaire in 301 individuals
Sleep questionnaire (six items) used to evaluate sleep problemsAge-dependent effects on DIMS, EDS and nightmares
DIMS prevalence ranged from 29–45% depending on age, sex and condition
Significant relationship between DMIS and EDS and the presence of chronic bronchitis, concomitant asthma and emphysemaKlink et al. [23] (1994) As for Klink and Quan [22], 1987
Questionnaire and spirometry used to identify patients with respiratory symptoms
443 individuals had one respiratory symptom
299 individuals had two respiratory symptomsPresence of DIMS and EDS were predicted by wheezing and sputum but not spirometry
Insomnia was reported in 39–53% depending on symptoms
EDS was reported in 12–23% of those with respiratory symptomsLewis et al. [24] (2009) Oximetry in 803 subjects from an outpatient COPD service; overnight oximetry in 59 patients who had resting oxygen saturation <95%
Questionnaires: CRQ, SF-36, PSQI, ESS and FOSQFocus on hypoxaemic component
Frequency of nocturnal desaturation (30% of the time <90%) estimated to be 4.8%
Desaturation was not associated with impaired HRQoL, sleep quality or daytime functionCormick et al. [25] (1986) Case–control study among 50 COPD patients and 40 age- matched controls
Sleep study in a subset of 16 patients with COPDProblems with DIMS (18–76%) and EDS (72%) over-represented in patients
Hypnotics used by 28% of patients versus 10% of controls
In a subgroup of 16 patients, sleep architecture disturbed in most patients: 12 out of 16 had hypoxaemia (>40% time at <90% saturation) during sleep with arousals occurring 3–46 times per hour (mean 15 times per hour)Valipour et al. [26] (2011) Case–control study among 52 patients with mild–moderate COPD and 52 matched controls
Sleep disorders questionnaire and polysomnographySleep efficiency, total sleep time and mean saturation lower among COPD patients versus controls
36% of COPD patients had problems falling asleep and 76% experienced frequent awakenings
Minimum oxygen independently predicted symptom scale scoresKinsman et al. [27] (1983) 146 patients with chronic bronchitis and emphysema were asked to rate the frequency with which 89 symptoms and experiences occurred during their breathing difficulties Symptom category “sleep difficulties” rated as third after dyspnoea and fatigue Karachaliou et al. [28] (2007) Multicentre questionnaire and spirometry study including physician-diagnosed asthma and COPD in 10 primary care centres n = 1501, aged 19–90 yrs Breathing pauses in 11% and EDS in 6.7%
Breathing pauses: OR 1.45 (95% CI 1.01–2.10) COPD versus asthma
EDS: OR 2.04 (95% CI 1.33–3.14) COPD versus asthmaTsai et al. [29] (2007) Multicentre cohort study examining treatment and outcome in 582 patients presenting with COPD exacerbation to the emergency room during the night or during the day Night-time patients (15%) had shorter duration of symptom exacerbation and were more likely to require noninvasive positive pressure ventilation
COPD characteristics did not differ between groupsDIMS: disorders of initiating and maintaining sleep; EDS: excessive daytime sleepiness; CRQ: Chronic Respiratory Questionnaire; SF-36: Short Form-36 questionnaire; PSQI: Pittsburgh Sleep Quality Index; ESS: Epworth Sleepiness Scale; FOSQ: Functional Outcomes of Sleep Questionnaire; HRQoL: health-related quality of life.
- Table 2. Consequences of nocturnal hypoxaemia and hypercapnia in chronic obstructive pulmonary disease (COPD)
Parameter/outcome Acute consequences Chronic consequences Sleep structure Altered in severe COPD, but inconsistent improvement of sleep with oxygen administration Worse sleep among pink puffers (mild desaturators) than blue bloaters (severe desaturators) Arrhythmias Observed during severe sleep desaturations; prevented by oxygen administration Risk not directly documented Pulmonary artery pressure Increased Inconsistent finding with regard to differences between desaturators and nondesaturators Diurnal blood gases Similar wake blood gas evolution among desaturators and nondesaturators; possible worsening of blood gases in severe COPD suggested by beneficial effects of ventilatory treatment Mortality Some suggestion that death may preferentially occur at night among patients with exacerbations (not systematically evaluated) Prognosis independent of nocturnal hypoxaemia measured in stable conditions Cardiovascular and cerebrovascular risk Increased ventricular ectopic events during periods of hypoxaemia Increased, possibly as a result of increased sympathetic activity and altered peripheral vascular tone due to recurrent nocturnal hypoxia Inflammatory mechanisms Pronounced activation among desaturators Data are taken from [34, 41–44].
- Table 3. Factors affecting daily breathlessness variation in 2,441 patients with severe chronic obstructive pulmonary disease
Factor OR (95% CI) p-value Age calculated for 10-yr changes 0.85 (0.75–0.96) 0.0106 Severity of breathlessness Moderately versus a little 1.47 (1.04–1.95) 0.0083 Very versus a little 2.85 (2.06–3.94) <0.0001 Extremely versus a little 2.56 (1.52–4.33) 0.0004 Maintenance treatment with only one long- acting bronchodilator (no versus yes) 2.06 (1.36–3.13) 0.0007 Physician activity (general practitioner versus specialist) 1.39 (1.08–1.78) 0.0099 Reproduced from [63] with permission from the publisher.
- Table 4. Night-time symptoms as secondary end-points in clinical trials of respiratory drugs for chronic obstructive pulmonary disease (COPD)
Citation Study drugs Night-time symptoms end-point Relevant results Welte et al. [68] (2009) Tiotropium plus budesonide/formoterol versus tiotropium alone Diary card including a five-point scale of sleep disturbance Tiotropium plus budesonide/formoterol improved awakening due to COPD Terzano et al. [69] (2008) Tiotropium with and without formoterol Diary card of night-time reliever use Evening dosing of tiotropium offered the greatest reduction in night-time reliever use Campbell et al. [70] (2005) Formoterol versus placebo Diary card including sleep disturbance and night-time reliever use Significant reduction in sleep disturbance and night-time reliever use with active treatment Welte et al. [71] (2008) Formoterol Diary card including a five-point scale of sleep disturbance based on the number and/or duration of awakenings and early awakenings Improvement in sleep disturbance with active treatment Tashkin et al. [72] (2009) Formoterol plus tiotropium versus tiotropium alone Diary card of night-time awakenings and reliever use Significantly greater decline in night-time
awakenings with the combination regimenRennard et al. [73] (2009) Budesonide plus formoterol versus formoterol alone Sleep score and per cent awakening-free nights Significant improvement in sleep score and per cent awakening-free nights with combination regimen Tashkin et al. [31] (2008) Budesonide plus formoterol in a single inhaler versus separate inhalers Diary card including a five-point scale of sleep disturbance; awakening-free nights Improvement in sleep score and awakening-free nights Partridge et al. [74] (2009) Budesonide plus formoterol versus salmeterol plus fluticasone E-diary card to record symptoms and basic morning activities Post-dose morning activity scores were significantly higher with budesonide plus formoterol after 1 week of dosing Anzueto et al. [30] (2009) Fluticasone plus salmeterol versus salmeterol alone Diary card of night-time awakenings Significant reduction in weekly night-time awakenings with combination regimen Zheng et al. [75] (2007) Fluticasone plus salmeterol versus placebo Diary card of night-time awakenings Significantly higher percentage of days without night-time awakenings with active treatment Make et al. [76] (2005) Fluticasone plus salmeterol versus placebo Diary card including a visual analogue scale of severity of sleep symptoms Significantly greater improvement in symptom-free nights, awakenings, and sleep symptom scores with combination regimen
Vol 20 Issue 121
Table of Contents
Night-time symptoms: a forgotten dimension of COPD
