Risk Factors for Recurrent Exacerbations in the General-Practitioner-Based Swiss Chronic Obstructive Pulmonary Disease (COPD) Cohort
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population and Study Design
- Tiffenau (FEV17FVC) < 70 without reversibility (increase in FEV1 after inhalation of a bronchodilator <200 mL and <12%);
- Age: >40 years;
- Both genders;
- Smokers or ex-smokers with at least 20 pack years;
- Informed consent.
- <40 years of age
- Tiffenau (FEV17FVC) > 70.
2.2. Assessment of Severity of COPD
2.3. COPD Assessment Test (CAT)
2.4. Modified Medical Research Council Dyspnea Scale
2.5. Statistical Analysis
2.6. Description of Recurrent Event Data
2.7. Analysis of Recurrent Event Data Using Negative Binomial Regression
2.8. Assessment of Performance
2.9. Nomogram
3. Results
3.1. Demographic and Baseline Data
3.2. Recurrent Event Process
3.3. Factors Associated with Recurrent Exacerbations
3.4. Nomogram
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
COPD | chronic obstructive pulmonary disease |
LABA | long-acting beta-agonists |
LAMA | long-acting muscarinic receptor antagonists |
ICS | inhaled corticosteroids |
SABA | short-acting bronchodilators |
mMRC | Modified Medical Research Council Dyspnea Scale |
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General Characteristics | All Patients | Training Dataset | Validation Dataset | p Value |
---|---|---|---|---|
N total | 256 | 192 | 64 | |
Age (years), Mean (SD) | 67.62 (10.17) | 67.86 (10.25) | 66.88 (9.95) | 0.496 |
BMI (kg/m2), Mean (SD) | 26.93 (6.07) | 26.88 (6.35) | 27.09 (5.21) | 0.786 |
Male sex | 162 (63.28%) | 120 (62.5%) | 42 (65.62%) | 0.765 |
Current smoker | 125 (48.83%) | 92 (47.92%) | 33 (51.56%) | 0.718 |
Lung function | ||||
FEV1 (% of predicted), Mean (SD) | 59.57 (18.15) | 59.79 (18.6) | 58.91 (16.87) | 0.725 |
FVC (% of predicted), Mean (SD) | 84.34 (22.51) | 84.83 (23.74) | 82.88 (18.43) | 0.496 |
FEV1/FVC, Mean (SD) | 56.09 (9.75) | 55.93 (9.65) | 56.57 (10.1) | 0.658 |
GOLD 1 | 38 (14.84%) | 31 (16.15%) | 7 (10.94%) | 0.708 |
GOLD 2 | 139 (54.3%) | 101 (52.6%) | 38 (59.38%) | |
GOLD 3 | 68 (26.56%) | 52 (27.08%) | 16 (25%) | |
GOLD 4 | 11 (4.3%) | 8 (4.17%) | 3 (4.69%) | |
Symptoms | ||||
mMRC dyspnea scale 0 | 22 (8.59%) | 15 (7.81%) | 7 (10.94%) | 0.344 |
mMRC dyspnea scale 1 | 103 (40.23%) | 73 (38.02%) | 30 (46.88%) | |
mMRC dyspnea scale 2 | 89 (34.77%) | 73 (38.02%) | 16 (25%) | |
mMRC dyspnea scale 3 | 35 (13.67%) | 25 (13.02%) | 10 (15.62%) | |
mMRC dyspnea scale 4 | 7 (2.73%) | 6 (3.12%) | 1 (1.56%) | |
COPD treatment | ||||
No LAMA, LABA, or ICS | 28 (10.94%) | 22 (11.46%) | 6 (9.38%) | 0.817 |
On short-acting bronchodilators (SABA) only | 77 (30.08%) | 60 (31.25%) | 17 (26.56%) | 0.582 |
On long-acting muscarinic antagonists (LAMA) | 43 (16.8%) | 32 (16.67%) | 11 (17.19%) | 1 |
On long-acting ß2-agonists (LABA) only | 4 (1.56%) | 3 (1.56%) | 1 (1.56%) | 1 |
On inhaled corticosteroids (ICS) only | 5 (1.95%) | 3 (1.56%) | 2 (3.12%) | 0.794 |
Inhaled combination therapy (LABA+ICS) | 36 (14.06%) | 24 (12.5%) | 12 (18.75%) | 0.299 |
Combination therapy (LABA+LAMA) | 79 (30.86%) | 63 (32.81%) | 16 (25%) | 0.31 |
LABA + LAMA + ICS | 63 (24.61%) | 46 (23.96%) | 17 (26.56%) | 0.802 |
On systemic corticosteroids | 7 (2.73%) | 6 (3.12%) | 1 (1.56%) | 0.825 |
O2 therapy previous year | 17 (6.64%) | 10 (5.21%) | 7 (10.94%) | 0.192 |
Physical activity | ||||
Exercise (at least twice a week) | 84 (32.81%) | 60 (31.25%) | 24 (37.5%) | 0.442 |
Pulmonary rehabilitation | 15 (5.86%) | 13 (6.77%) | 2 (3.12%) | 0.442 |
Comorbidities | ||||
Asthma | 31 (12.11%) | 21 (10.94%) | 10 (15.62%) | 0.439 |
Hypertension | 128 (50%) | 98 (51.04%) | 30 (46.88%) | 0.665 |
Coronary heart disease | 31 (12.11%) | 24 (12.5%) | 7 (10.94%) | 0.912 |
Heart failure | 13 (5.08%) | 9 (4.69%) | 4 (6.25%) | 0.869 |
Peripheral artery disease | 21 (8.2%) | 18 (9.38%) | 3 (4.69%) | 0.357 |
Cerebrovascular Insult | 8 (3.12%) | 5 (2.6%) | 3 (4.69%) | 0.678 |
Diabetes | 31 (12.11%) | 23 (11.98%) | 8 (12.5%) | 1 |
Cancer | 10 (3.91%) | 9 (4.69%) | 1 (1.56%) | 0.456 |
Exacerbation history over the past year | 66 (25.78%) | 49 (25.52%) | 17 (26.56%) | 1 |
Outcome | ||||
Exacerbation count: 0 | 193 (75.39%) | 147 (76.56%) | 46 (71.88%) | 0.123 |
Exacerbation count: 1 | 42 (16.41%) | 33 (17.19%) | 9 (14.06%) | |
Exacerbation count: 2 | 15 (5.86%) | 9 (4.69%) | 6 (9.38%) | |
Exacerbation count: 3 | 3 (1.17%) | 1 (0.52%) | 2 (3.12%) | |
Exacerbation count: 5 | 2 (0.78%) | 2 (1.04%) | 0 (0%) | |
Exacerbation count: 7 | 1 (0.39%) | 0 (0%) | 1 (1.56%) | |
Follow-up time (years), Mean (SD) | 193 (75.39%) | 147 (76.56%) | 46 (71.88%) | 0.123 |
Factors | IRR | 95% CI Lower | 95% CI Upper | p-Value |
---|---|---|---|---|
LABA/LAMA/ICS | 2.5 | 1.34 | 4.67 | 0.004 |
Exacerbation history over the past year | 2.06 | 1.08 | 3.93 | 0.027 |
mMRC dyspnea scale (per score) | 1.48 | 1.07 | 2.07 | 0.022 |
Asthma | 1.36 | 0.53 | 3.37 | 0.517 |
Age (per 10 years) | 1.22 | 0.88 | 1.71 | 0.208 |
On SABA only | 1.21 | 0.62 | 2.32 | 0.574 |
BMI (per 10 kg/m2) | 0.88 | 0.53 | 1.43 | 0.614 |
Hypertension | 0.88 | 0.48 | 1.63 | 0.688 |
Diabetes | 0.86 | 0.29 | 2.3 | 0.773 |
On LAMA only | 0.83 | 0.34 | 1.92 | 0.666 |
Current smoker at baseline | 0.82 | 0.44 | 1.51 | 0.522 |
On LABA/LAMA | 0.78 | 0.4 | 1.52 | 0.479 |
Male vs female sex | 0.76 | 0.41 | 1.42 | 0.381 |
Coronary heart disease | 0.75 | 0.25 | 2 | 0.582 |
Baseline FEV1 (per 10% of predicted) | 0.74 | 0.62 | 0.88 | 0.001 |
On LABA + ICS | 0.36 | 0.08 | 1.15 | 0.116 |
IRR | 2.50% | 97.50% | p-Value | |
---|---|---|---|---|
Baseline FEV1 (per 10% of predicted) | 0.81 | 0.68 | 0.97 | 0.027 |
mMRC dyspnea scale (per score) | 1.3 | 0.94 | 1.81 | 0.123 |
LABA/ICS | 0.43 | 0.1 | 1.33 | 0.183 |
LABA/LAMA/ICS | 1.69 | 0.9 | 3.14 | 0.102 |
Exacerbation history in the past year | 1.65 | 0.89 | 3.02 | 0.108 |
Number of Exacerbations | AUC | AUC 95% Lower Limit | AUC 95% Lower Limit | Sensitivity at Best Threshold * | Specificity at Best Threshold * |
---|---|---|---|---|---|
Training | |||||
≥1 | 0.69 | 0.60 | 0.78 | 0.67 | 0.68 |
≥2 | 0.86 | 0.76 | 0.96 | 0.83 | 0.82 |
≥3 | 0.88 | 0.77 | 0.99 | 1.00 | 0.79 |
Validation | |||||
≥1 | 0.71 | 0.56 | 0.85 | 0.67 | 0.65 |
≥2 | 0.78 | 0.62 | 0.93 | 0.89 | 0.55 |
≥3 | 0.67 | 0.32 | 1.00 | 1.00 | 0.38 |
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Abu Hussein, N.S.; Giezendanner, S.; Urwyler, P.; Bridevaux, P.-O.; Chhajed, P.N.; Geiser, T.; Joos Zellweger, L.; Kohler, M.; Miedinger, D.; Pasha, Z.; et al. Risk Factors for Recurrent Exacerbations in the General-Practitioner-Based Swiss Chronic Obstructive Pulmonary Disease (COPD) Cohort. J. Clin. Med. 2023, 12, 6695. https://doi.org/10.3390/jcm12206695
Abu Hussein NS, Giezendanner S, Urwyler P, Bridevaux P-O, Chhajed PN, Geiser T, Joos Zellweger L, Kohler M, Miedinger D, Pasha Z, et al. Risk Factors for Recurrent Exacerbations in the General-Practitioner-Based Swiss Chronic Obstructive Pulmonary Disease (COPD) Cohort. Journal of Clinical Medicine. 2023; 12(20):6695. https://doi.org/10.3390/jcm12206695
Chicago/Turabian StyleAbu Hussein, Nebal S., Stephanie Giezendanner, Pascal Urwyler, Pierre-Olivier Bridevaux, Prashant N. Chhajed, Thomas Geiser, Ladina Joos Zellweger, Malcolm Kohler, David Miedinger, Zahra Pasha, and et al. 2023. "Risk Factors for Recurrent Exacerbations in the General-Practitioner-Based Swiss Chronic Obstructive Pulmonary Disease (COPD) Cohort" Journal of Clinical Medicine 12, no. 20: 6695. https://doi.org/10.3390/jcm12206695
APA StyleAbu Hussein, N. S., Giezendanner, S., Urwyler, P., Bridevaux, P.-O., Chhajed, P. N., Geiser, T., Joos Zellweger, L., Kohler, M., Miedinger, D., Pasha, Z., Thurnheer, R., von Garnier, C., & Leuppi, J. D. (2023). Risk Factors for Recurrent Exacerbations in the General-Practitioner-Based Swiss Chronic Obstructive Pulmonary Disease (COPD) Cohort. Journal of Clinical Medicine, 12(20), 6695. https://doi.org/10.3390/jcm12206695