Table 2 Studies investigating associations between COPD symptoms and other factors

 Miravitlles et al. Respir Med. 2007 [11]

Patient questionnaire (daily wellbeing and COPD symptoms)

Increased coughing, followed by increasing shortness of breath, fatigue, and increased production of sputum were reported as having a strong impact on wellbeing

 Jones et al. Prim Care Respir J. 2012 [4]

SGRQ (quality of life)

CAT (quality of life)

MRC scale (dyspnea)

Patient questionnaire (symptoms)

Dyspnea grade, PCP-rated COPD severity, sputum production and number of comorbidities were significantly associated with SGRQ and CAT score (all p < 0.0001)

 Price et al. Int J Chron Obstruct Pulmon Dis. 2013 [13]

EQ-5D (quality of life)

Physician record (COPD symptoms time of day)

Patients with physician-reported nighttime symptoms had significantly poorer quality of life (p < 0.0001)

 Monteagudo et al. Respir Med. 2013 [12]

SGRQ (quality of life)

Patient interview (chronic respiratory symptoms)

Cough and sputum and increased dyspnea were associated with a significant worsening of HRQoL (all p < 0.001)

 Miravitlles et al. Respir Res. 2014 [3]

CAT score (quality of life)

Patient questionnaire (COPD symptoms)

Overall health status was significantly lower in patients with at least one symptom in the morning, daytime, or nighttime (p < 0.001)

 Stephenson et al. Int J Chron Obstruct Pulmon Dis. 2015 [27]

CAT score (quality of life)

Patient questionnaire (COPD symptoms)

Patients with both nighttime and early-morning symptoms were more likely to have poorer health status

(OR 8.03; 95% CI 4.33, 14.89)

 Partridge et al. Curr Med Res Opin. 2009 [17]

Patient questionnaire (COPD symptoms)

The impact of COPD symptoms on

morning activities is substantial, with dyspnea being the most problematic

 Kessler et al. Eur Respir J. 2011 [5]

Patient questionnaire (COPD symptoms and impact on daily activities)

Morning symptoms of COPD had the greatest impact on daily living activities

 O’Hagan and Chavannes. Curr Med Res Opin. 2014 [28]

Patient questionnaire (COPD symptoms and impact on daily activities)

With morning symptoms, routine activities took 10–15 min longer and more strenuous activities around 30 min longer

 Stephenson et al. Int J Chron Obstruct Pulmon Dis. 2015 [27]

Patient questionnaire (COPD symptoms and limitation of activities)

60.4% of patients reported limiting their morning activity due to early-morning symptoms

 Miravitlles et al. Respir Res. 2014 [3]

Patient questionnaire (COPD symptoms time of day and physical activity levels)

A higher proportion of patients who were

sedentary had symptoms in the morning, daytime, and nighttime compared with active patients

 Ng et al. Arch Intern Med. 2007 [46]

HADS (depression)

SGRQ (COPD symptom burden and QoL)

Increased symptom burden in patients with depression (p < 0.001)

 Doyle et al. Int J Psychiatry Med. 2013 [16]

State-Trait Anxiety Inventory (anxiety)

Beck Depression Inventory (depression)

Brief Fatigue Inventory (fatigue)

SGRQ (COPD symptoms)

UCSD Shortness of Breath Questionnaire (dyspnea)

6MWT (functional capacity)

Anxiety and depression associated with higher fatigue, dyspnea, and frequency of COPD symptoms (all p < 0.001); more so in patients with lower functional capacity (p = 0.02–0.009)

 Miravitlles et al. Respir Med. 2014 [44]

Beck Depression Inventory (depression)

mMRC scale (dyspnea)

Greater dyspnea in patients with depression vs no depression (mean dyspnea grade: 2.07 vs 1.32; p < 0.0001)

 Miravitlles et al. Respir Res. 2014 [3]

HADS (depression)

Patient questionnaire (COPD symptoms time of day)

Experiencing symptoms in the morning, daytime, and nighttime was associated with anxiety and depression (p < 0.001)

 Martinez Rivera et al. Lung 2016 [45]

HADS (depression)

MRC scale (dyspnea)

Greater dyspnea in patients with depression

 Partridge et al. Curr Med Res Opin. 2009 [17]

Patient questionnaire (COPD symptoms)

Patients experiencing general fatigue and tiredness reported worse nighttime symptoms (p = 0.003)

 Kessler et al. Eur Respir J. 2011 [5]

Patient interview (sleep and COPD symptoms)

A quarter of the total study population reported that their COPD symptoms had affected sleep quality

 Scharf et al. Int J Chron Obstruct Pulmon Dis. 2011 [51]

Pittsburgh Sleep Quality Index (sleep)

Sleep Symptom Questionnaire (nighttime sleep symptoms of COPD)

Sleep time correlated with the number of nocturnal symptoms such as wheezing, worrying, and uncontrolled thoughts (p < 0.0001). Specific respiratory symptoms were not significantly associated with low sleep times

 Omachi et al. Sleep Med. 2012 [52]

Medical Outcomes Study sleep battery (sleep)

MRC scale (dyspnea)

Patient interview (dyspnea and cough)

Patients with cough symptoms had three-fold greater likelihood of disturbed sleep (p = 0.034)

The degree of dyspnea was associated with a higher likelihood of disturbed sleep (p = 0.004)

 Price et al. Int J Chron Obstruct Pulmon Dis. 2013 [13]

Jenkins Sleep Questionnaire

Seven-point Likert scale

Frequency of nocturnal awakening

Patients with nighttime symptoms are significantly more likely to experience sleep disturbance vs those without nighttime symptoms (p < 0.0001)

 Miravitlles et al. Respir Res. 2014 [3]

COPD and Asthma Sleep Impact Scale (sleep quality)

Symptom questionnaire (COPD symptoms time of day)

Experiencing symptoms in the morning, daytime, and nighttime was associated with sleep impairment (p < 0.001)

 Nishimura et al. Chest 2002 [54]

Modified 5-point grading scale (dyspnea)

5-year cumulative survival rate (mortality)

The level of dyspnea was associated with a lower 5-year survival rate (p < 0.001)

 Burgel et al. Chest 2009 [56]

Patient questionnaire (COPD symptoms and exacerbations) Medical records (exacerbations)

Productive cough was independently associated with frequent exacerbations (≥2 in the previous year) (p < 0.0001)

 Lange et al. Eur Respir J. 2014 [21]

Patient questionnaire (COPD symptoms) Hospital admissions data (previous and follow-up exacerbations)

Patients with nighttime dyspnea were more likely to have had ≥2 exacerbations in the previous year (p < 0.001). Nighttime symptoms were associated with future exacerbations (HR 2.3; 95% CI 1.7, 3.0)

 Putcha et al. COPD 2014 [58]

Patient questionnaire (COPD symptoms) Mortality data (mortality)

Cough and phlegm symptoms together were associated with an increased risk of mortality (HR 1.27; 95% CI 1.02, 1.59)

 Lindberg et al. Respir Med. 2015 [57]

Patient interview (COPD symptoms and exacerbations) Mortality data (mortality)

Patients with a productive cough have an increased risk of exacerbations (OR 9.25; 95% CI 6.23, 13.75), and a significantly increased risk of mortality (HR 1.48; 95% CI 1.13, 1.94)

 Miravitlles et al. COPD 2016 [25]

Patient questionnaire (COPD symptoms) Hospital admissions data (follow-up exacerbations)

Early-morning and daytime symptoms were associated with exacerbations during follow-up (both p < 0.01), however significance was not maintained when adjusted for potential confounding factors