Mucolytic Agents and Statins Use is Associated with a Lower Risk of Acute Exacerbations in Patients with Bronchiectasis-Chronic Obstructive Pulmonary Disease Overlap
Abstract
:1. Introduction
2. Methods
2.1. Data Source
2.2. Study Design and Population
2.3. Potential Confounders and Classification of Severity
2.4. Effect of Exposure to Co-Medications
2.5. Statistical Analysis
3. Results
3.1. Clinical Characteristics of the Study Population
3.2. The Effect of Bronchiectasis on Acute Exacerbations and Mortality
3.3. Effects of Co-medications on Acute Exacerbations and Mortality
3.4. Sensitivity and Subgroup Analyses for the Effects of Co-Medications on Acute Exacerbations
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Acknowledgements
Conflict of interest
References
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Characteristics | BCO Cohort | COPD Alone Cohort | p Value | ||
---|---|---|---|---|---|
n | % | n | % | ||
n | 831 | 3321 | |||
Age, years (mean ± SD) | 68.70 ± 12.14 | 68.61 ± 12.08 | 0.8433 | ||
Age | 0.9822 | ||||
40–49 | 62 | 7.46% | 248 | 7.47% | |
50–59 | 136 | 16.37% | 564 | 16.98% | |
60–69 | 207 | 24.91% | 834 | 25.11% | |
70–79 | 254 | 30.57% | 1016 | 30.59% | |
≥80 | 172 | 20.70% | 659 | 19.84% | |
Sex | 0.9741 | ||||
Male | 549 | 66.06% | 2196 | 66.12% | |
Female | 282 | 33.94% | 1125 | 33.88% | |
Follow-up, years (mean ± SD) § | 4.53 ± 3.00 | 5.22 ± 2.95 | <0.0001 | ||
COPD severity † | |||||
COPD-related ED visits, n (%) | <0.0001 | ||||
0 | 751 | 90.37% | 3214 | 96.78% | |
≥1 | 80 | 9.63% | 107 | 3.22% | |
COPD-related hospitalizations, n (%) | <0.0001 | ||||
0 | 657 | 79.06% | 2943 | 88.62% | |
≥1 | 174 | 20.94% | 378 | 11.38% | |
COPD medications ‡, n (%) | <0.0001 | ||||
0–2 | 525 | 63.18% | 2830 | 85.22% | |
≥3 | 306 | 36.82% | 491 | 14.78% | |
Comorbidities # | |||||
Diabetes mellitus | 152 | 18.29% | 622 | 18.73% | 0.7718 |
Cardiovascular disease | 476 | 57.28% | 1846 | 55.59% | 0.3788 |
Stroke | 166 | 19.98% | 513 | 15.45% | 0.0016 |
Chronic kidney disease | 32 | 3.85% | 119 | 3.58% | 0.7126 |
Antecedent Pneumonia | 289 | 34.78% | 317 | 9.55% | <0.0001 |
Malignancy | 181 | 21.78% | 361 | 10.87% | <0.0001 |
Medications during the follow-up period * | |||||
Statins | 145 | 17.45% | 851 | 25.62% | <0.0001 |
Macrolides | 118 | 14.20% | 163 | 4.91% | <0.0001 |
Mucolytic agents | 712 | 85.68% | 2255 | 67.90% | <0.0001 |
Medications, before the first AE $ | |||||
Statins | 113 | 13.60% | 805 | 24.24% | <0.0001 |
Macrolides | 70 | 8.42% | 121 | 3.64% | <0.0001 |
Mucolytic agents | 638 | 76.77% | 2091 | 62.96% | <0.0001 |
BCO Cohort | COPD Alone Cohort | Rate Ratio | p Value * | |||
---|---|---|---|---|---|---|
n | Rate § | n | Rate § | |||
Total exacerbations † | 1224 | 32.53 | 1651 | 9.52 | 3.42 (3.17–3.68) | <0.0001 |
Moderate exacerbations † | ||||||
OPD visits | 841 | 22.35 | 1080 | 6.23 | 3.59 (3.28–3.93) | <0.0001 |
ED visits | 43 | 1.14 | 71 | 0.41 | 2.79 (1.87–4.13) | <0.0001 |
Severe exacerbations † | ||||||
Hospital admissions | 340 | 9.04 | 500 | 2.88 | 3.14 (2.72–3.61) | <0.0001 |
ICU admissions | 65 | 1.73 | 69 | 0.40 | 4.34 (3.05–6.18) | <0.0001 |
Hospitalization days | 6146 | 163.32 | 8395 | 48.39 | 3.38 (3.27–3.49) | <0.0001 |
Drugs for exacerbations, (mean ± SD) | ||||||
Steroids ‡ (mg) | 281.2 ± 342.9 | 208.0 ± 273.5 | <0.0001 | |||
Antibiotics (days) | 14.90 ± 14.78 | 12.63 ± 11.92 | 0.0011 | |||
Anti-pseudomonal FQs #, event (%) | 15.03% | 8.96% | <0.0001 | |||
Mucolytic agents, event (%) | 60.78% | 56.75% | 0.0301 |
Variables | BCO Cohort | COPD Alone Cohort | ||
---|---|---|---|---|
HR (95% CI) | p | HR (95% CI) | p | |
Medications, before first AE | ||||
Statins (total) | 0.44 (0.29–0.65) | <0.0001 | 0.35 (0.26–0.46) | <0.0001 |
Statins, 28–90 days | 0.77 (0.38–1.57) | 0.4647 | 0.71 (0.46–1.08) | 0.1071 |
Statins, >90 days | 0.37 (0.23–0.59) | <0.0001 | 0.26 (0.18–0.37) | <0.0001 |
Macrolides (total) | 0.85 (0.54–1.32) | 0.4611 | 0.46 (0.25–0.83) | 0.0103 |
Macrolides, 28–90 days | 0.94 (0.58–1.52) | 0.7947 | 0.41 (0.21–0.79) | 0.0077 |
Macrolides, >90 days | 0.53 (0.17–1.67) | 0.2795 | 0.99 (0.25–3.98) | 0.9861 |
Mucolytic agents (total) | 0.58 (0.45–0.75) | <0.0001 | 0.73 (0.61–0.86) | 0.0003 |
Mucolytic agents, 28–90 days | 0.80 (0.60–1.08) | 0.1504 | 0.82 (0.66–1.01) | 0.0638 |
Mucolytic agents, >90 days | 0.48 (0.36–0.63) | <0.0001 | 0.67 (0.55–0.82) | <0.0001 |
Variables | BCO Cohort | COPD Cohort | ||
---|---|---|---|---|
Adjusted HR (95% CI) | p | Adjusted HR (95% CI) | p | |
Medications, before first AE | ||||
Statins | ||||
Simvastatin | 0.38 (0.19–0.77) | 0.0066 | 0.26 (0.15–0.46) | <0.0001 |
Lovastatin | 0.23 (0.07–0.72) | 0.0113 | 0.43 (0.23–0.78) | 0.0053 |
Pravastatin | 0.68 (0.28–1.68) | 0.4067 | 0.58 (0.30–1.13) | 0.1078 |
Fluvastatin | 0.57 (0.23–1.39) | 0.2144 | 0.31 (0.15–0.66) | 0.0024 |
Atorvastatin | 0.28 (0.15–0.53) | <0.0001 | 0.34 (0.23–0.52) | <0.0001 |
Rosuvastatin | 0.42 (0.20–0.89) | 0.0229 | 0.25 (0.13–0.46) | <0.0001 |
Macrolides | ||||
Erythromycin | 0.89 (0.45–1.74) | 0.7303 | 0.85 (0.35–2.05) | 0.7102 |
Azithromycin | 0.30 (0.04–2.13) | 0.2278 | N/A | N/A |
Clarithromycin | 1.03 (0.42–2.50) | 0.9564 | 0.77 (0.32–1.86) | 0.5595 |
Mucolytic agents | ||||
N-acetylcysteine | 0.75 (0.58–0.98) | 0.0359 | 0.84 (0.68–0.98) | 0.0346 |
Carbocysteine | 0.57 (0.34–0.96) | 0.0349 | 0.79 (0.54–1.14) | 0.2033 |
Ambroxol | 0.60 (0.48–0.76) | <0.0001 | 0.78 (0.66–0.93) | 0.0055 |
Iodinated glycerol | 0.72 (0.41–1.26) | 0.2522 | 1.01 (0.68–1.51) | 0.9444 |
Bromhexine | 0.60 (0.45–0.80) | 0.0004 | 0.84 (0.68–1.02) | 0.0843 |
Mesna | 0.50 (0.07–3.62) | 0.4949 | 0.55 (0.08–3.96) | 0.5563 |
Eprazinone | 0.63 (0.41–0.98) | 0.0413 | 0.50 (0.33–0.78) | 0.0022 |
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Su, V.Y.-F.; Perng, D.-W.; Chou, T.-C.; Chou, Y.-C.; Chang, Y.-L.; Hsu, C.-C.; Chou, C.-L.; Lee, H.-C.; Chen, T.-J.; Hu, P.-W. Mucolytic Agents and Statins Use is Associated with a Lower Risk of Acute Exacerbations in Patients with Bronchiectasis-Chronic Obstructive Pulmonary Disease Overlap. J. Clin. Med. 2018, 7, 517. https://doi.org/10.3390/jcm7120517
Su VY-F, Perng D-W, Chou T-C, Chou Y-C, Chang Y-L, Hsu C-C, Chou C-L, Lee H-C, Chen T-J, Hu P-W. Mucolytic Agents and Statins Use is Associated with a Lower Risk of Acute Exacerbations in Patients with Bronchiectasis-Chronic Obstructive Pulmonary Disease Overlap. Journal of Clinical Medicine. 2018; 7(12):517. https://doi.org/10.3390/jcm7120517
Chicago/Turabian StyleSu, Vincent Yi-Fong, Diahn-Warng Perng, Ting-Chun Chou, Yueh-Ching Chou, Yuh-Lih Chang, Chia-Chen Hsu, Chia-Lin Chou, Hsin-Chen Lee, Tzeng-Ji Chen, and Po-Wei Hu. 2018. "Mucolytic Agents and Statins Use is Associated with a Lower Risk of Acute Exacerbations in Patients with Bronchiectasis-Chronic Obstructive Pulmonary Disease Overlap" Journal of Clinical Medicine 7, no. 12: 517. https://doi.org/10.3390/jcm7120517
APA StyleSu, V. Y.-F., Perng, D.-W., Chou, T.-C., Chou, Y.-C., Chang, Y.-L., Hsu, C.-C., Chou, C.-L., Lee, H.-C., Chen, T.-J., & Hu, P.-W. (2018). Mucolytic Agents and Statins Use is Associated with a Lower Risk of Acute Exacerbations in Patients with Bronchiectasis-Chronic Obstructive Pulmonary Disease Overlap. Journal of Clinical Medicine, 7(12), 517. https://doi.org/10.3390/jcm7120517