Introduction
Methods
Study cohort
Microbiological sample collection
General measurements
Outcomes
Statistical analysis
Results
General data on study cohort
Variables | Normal LHS (≤ 7 days) (n = 213) | Prolonged LHS (> 7 days) (n = 224) | p value |
---|---|---|---|
Domiciliary medications
| |||
Age, years | 73 [64.5; 78] | 72 [64; 78] | 0.857 |
Male, % | 82 | 80 | 0.637 |
BMI, kg/m2 | 27 [24.2; 29.4] | 27.6 [23.4; 31.5] | 0.486 |
Smoking habit: Current/Former, % | 41/59 | 39/61 | 0.598 |
Pack/year | 50 [40; 80] | 60 [40; 80] | 0.797 |
FEV1, % predicted | 44 [33; 63] | 42 [30; 58] | 0.126 |
FEV1/FVC | 49.5 [38.7; 62] | 49 [36; 62.7] | 0.823 |
GOLD 2017 stages: A/B/C/D, % | 32/32/15/21 | 18/39/12/31 |
0.015
|
LTOT, % | 22 | 32 |
0.013
|
mMRC dyspnoea grade | 2 [1; 3] | 2 [1; 4] |
0.001
|
COPD-SS severity questionnaire | 13 [8; 18] | 14 [9; 19] | 0.108 |
Charlson index | 2 [1; 3] | 2 [1; 3] | 0.750 |
Ischaemic heart disease, % | 11 | 9 | 0.501 |
Congestive heart disease, % | 9 | 18 |
0.008
|
Diabetes, % | 21 | 23 | 0.618 |
Chronic kidney failure, % | 4 | 7 | 0.257 |
Season of admission: Winter/Spring/Summer/Autumn, % | 40/14/29/17 | 45/16/25/14 | 0.508 |
Period of admission: years 2009–2011/2012–2104/2015–2017, % | 61/31/8 | 58/30/12 | 0.463 |
Previous AECOPDa | 0 [0; 1] | 0 [0; 2] | 0.286 |
Patients with ≥2 previous AECOPDa, % | 24 | 27 | 0.501 |
Previous AECOPD requiring hospitalisationa | 0 [0; 1] | 0 [0; 1] |
0.030
|
Patients with ≥1 previous AECOPD requiring hospitalisationa, % | 28 | 37 |
0.029
|
Onset of symptoms until admission, days | 4 [2; 7] | 5 [3; 7.75] |
0.035
|
Use of antibiotics previous admission
| |||
In a period of one week before, % | 24 | 23 | 0.924 |
Days of treatment | 7 [3; 10] | 6 [3; 7] | 0.625 |
Penicillins/Fluoroquinolones/Macrolides/Cephalosporins/Others, % | 30/48/11/2/9 | 24/40/18/11/7 | 0.248 |
In a period of three months before, % | 40 | 53 |
0.044
|
Penicillins/Fluoroquinolones/Macrolides/Cephalosporins/Others, % | 23/63/5/0/9 | 34/45/10/8/3 | 0.149 |
Use of other drugs in a period of two weeks before admission
| |||
Systemic corticosteroids, % | 12 | 13 | 0.867 |
Salbutamol, % | 4 | 14 |
0.001
|
Ipratropium bromide, % | 5 | 13 |
0.005
|
Domiciliary medications | |||
Salbutamol only, % | 3 | 3 | 0.922 |
Anticholinergic only, % | 5 | 5 | 0.819 |
LABA + Anticholinergic, % | 2 | 1 | > 0.999 |
LABA + ICS, % | 3 | 2 | > 0.999 |
Anticholinergic + ICS, % | 2 | 1 | > 0.999 |
LABA + Anticholinergic + ICS, % | 36 | 37 | 0.828 |
Clinical, laboratory and microbiological variables
Variables | Normal LHS (≤ 7 days) (n = 213) | Prolonged LHS (> 7 days) (n = 224) | p value |
---|---|---|---|
Respiratory rate, b/min | 24 [20; 28] | 24 [20; 28] | 0.482 |
Heart rate, b/min | 91.5 [83; 102.5] | 95 [80; 108] | 0.293 |
Body temperature, °C | 36.4 [35.9; 37] | 36.3 [36; 36.8] | 0.569 |
SBP, mmHg | 140 [120; 155] | 135.5 [124; 156] | 0.719 |
DBP, mmHg | 75 [68; 86] | 76 [68; 87] | 0.895 |
Laboratory variables at admission
| |||
Leucocytes, 109/l | 10.1 [7.9; 14] | 10.1 [7.7; 13.6] | 0.464 |
Haematocrit, % | 43 [39; 47] | 43 [40; 47] | 0.425 |
Haemoglobin, g/L | 138 [125; 151] | 140 [127; 153] | 0.738 |
C-reactive protein, mg/dL | 4.1 [1.3; 10.1] | 3.6 [1.1; 9.7] | 0.412 |
Glucose, mg/dL | 123 [108; 152.7] | 126 [107.7; 166] | 0.485 |
Creatinine, mg/dL | 0.9 [0.8; 1.1] | 0.9 [0.7; 1.1] |
0.041
|
Laboratory variables at day 3
| |||
Leucocytes, 109/l | 10.6 [8.3; 13.4] | 10.7 [8.1; 13] | 0.922 |
Haematocrit, % | 41 [38; 44] | 41 [37; 45] | 0.685 |
Haemoglobin, g/L | 131 [119; 143] | 131 [118; 143] | 0.436 |
C-reactive protein, mg/dL | 1.4 [0.5; 4.1] | 0.9 [0.3; 2.9] | 0.161 |
Glucose, mg/dL | 116 [96; 153] | 123 [100.5; 161] | 0.096 |
Creatinine, mg/dL | 0.9 [0.7; 1.2] | 0.8 [0.7; 1] |
0.027
|
Treatments during hospitalisation
| |||
Systemic corticosteroids, % | 91 | 92 | 0.631 |
Antibiotics, % | 84 | 88 | 0.304 |
Number of antibiotics used, 0/1/≥2, % | 16/64/20 | 12/64/24 | 0.383 |
Duration of antibiotic treatment, days | 7 [5; 10] | 7 [6; 10] | 0.375 |
Penicillins, % | 16 | 19 | 0.498 |
Fluoroquinolones, % | 57 | 45 |
0.023
|
Macrolides, % | 2 | 2 | > 0.999 |
Cephalosporins, % | 1 | 5 |
0.035
|
Carbapenems, % | 0 | 1 | 0.501 |
Sputum sample collected in the previous year the hospitalisation | Sputum sample collectedduring the hospitalisation | |||||||
---|---|---|---|---|---|---|---|---|
Number of cases | Normal LHSa (≤ 7 days) | Prolonged LHSa (> 7 days) | p value | Number of cases | Normal LHSa (≤ 7 days) | Prolonged LHSa (> 7 days) | p value | |
Patients with positive cultures | 63 | 33 | 67 |
0.008
| 91 | 35 | 43 | 0.179 |
Number of pathogens: 0 | 373 | 51 | 49 |
0.031
| 346 | 51 | 49 | 0.138 |
1 | 43 | 33 | 67 | 89 | 39 | 61 | ||
≥ 2 | 20 | 35 | 65 | 2 | 50 | 50 | ||
Pseudomonas aeruginosa
| 16 | 13 | 87 |
0.041
| 25 | 12 | 88 |
0.001
|
Pseudomonas aeruginosa colonisationc | – | – | – | – | 9 | 0 | 100 |
0.002
|
Haemophilus influenzae
| 5 | 60 | 40 | 0.323 | 16 | 31 | 69 | 0.454 |
Streptococcus pneumoniae
| 7 | 43 | 57 | 0.677 | 18 | 61 | 39 |
0.037
|
Streptococcus spp.
| 5 | 20 | 80 | 0.657 | – | – | – | – |
Staphylococcus spp.
| 4 | 50 | 50 | 0.595 | 7 | 29 | 71 | 0.699 |
Pasteurella
| – | – | – | – | 2 | 50 | 50 | > 0.999 |
Moraxella catarrhalis
| 3 | 67 | 33 | 0.256 | 3 | 100 | 0 | 0.059 |
Candida spp.
| – | – | – | – | 2 | 50 | 50 | > 0.999 |
Aspergillus
| – | – | – | – | 2 | 50 | 50 | > 0.999 |
Serratia
| – | – | – | – | 1 | 0 | 100 | > 0.999 |
Escherichia coli
| 1 | 0 | 100 | > 0.999 | – | – | – | – |
Mycobacterium no-TBC
| – | – | – | – | 1 | 100 | 0 | 0.396 |
Polymicrobial | 20 | 35 | 65 | 0.848 | 8 | 50 | 50 | 0.708 |
Classification according to the conventional treatmentb: MSCT | 31 | 45 | 55 |
0.026
| 51 | 51 | 49 |
0.014
|
MRCT | 20 | 15 | 85 | 30 | 23 | 77 | ||
MRCT colonisationc | – | – | – | – | 10 | 10 | 90 |
0.009
|
Influenza B virus
| – | – | – | – | 2 | 50 | 50 | > 0.999 |
Respiratory syncytial virus
| – | – | – | – | 7 | 43 | 57 | > 0.999 |
Rhinovirus
| – | – | – | – | 7 | 29 | 71 | 0.450 |
Parainfluenza virus type 1
| – | – | – | – | 3 | 67 | 33 | 0.615 |
Parainfluenza virus type 3
| – | – | – | – | 3 | 0 | 100 | 0.499 |
Parainfluenza virus type 4
| – | – | – | – | 1 | 100 | 0 | 0.487 |
Study outcomes
Variables | Normal LHS (≤ 7 days) (n = 213) | Prolonged LHS (> 7 days) (n = 224) | p value |
---|---|---|---|
NIMV, % | 11 | 31 |
< 0.001
|
IMV, % | 0 | 7 |
< 0.001
|
ICU admission, % | 5 | 19 |
< 0.001
|
Mortality at 6-months, % | 4 | 14 |
< 0.001
|
Survival time | 176.3 [173.8 to 178.8] | 168.5 [164.3 to 172.7] |
0.001
|
Cumulative mortality at 1-year, % | 11 | 25 |
< 0.001
|
Survival time | 342.5 [334.4 to 350.5] | 313.6 [301.1 to 326.2] |
< 0.001
|
Cumulative mortality at 3-years, % | 37 | 48 |
0.036
|
Survival time | 904.6 [862.3 to 946.8] | 783.8 [730.6 to 837.1] |
0.007
|
Prediction analyses
Variable | Univariate | Multivariate | ||||
---|---|---|---|---|---|---|
OR | 95% CI | p value | OR | 95% CI | p | |
mMRC dyspnoea score (≥ 2) | 2.07 | 1.29 to 3.32 |
0.002
| 2.24 (2.76) | 1.34 to 3.74 (1.54 to 4.92) |
0.002 (0.001)
|
GOLD 2017 stages: Stage A | 1.00 | |||||
Stage B | 2.24 | 1.22 to 4.08 |
0.009
| – | – | – |
Stage C | 1.48 | 0.68 to 3.20 | 0.322 | – | – | – |
Stage D | 2.60 | 1.35 to 4.98 |
0.004
| – | – | – |
No. of previous AECOPD requiring hospitalisation (≥ 1) | 1.57 | 1.05 to 2.35 |
0.030
| – | – | – |
Use of LTOT | 1.72 | 1.12 to 2.64 |
0.014
| – | – | – |
Onset of symptoms until admission (≥ 7 days) | 1.49 | 0.99 to 2.42 |
0.053
| – | – | – |
Use of antibiotics three months before admission | 1.72 | 1.01 to 2.93 |
0.044
| |||
Use of salbutamol two weeks before admission | 3.44 | 1.59 to 7.43 |
0.002
| – | – | – |
Use of ipratropium two weeks before admission | 2.84 | 1.34 to 6.01 |
0.006
| – | – | – |
COPD-SS (≥ 15 score) | 1.39 | 0.94 to 2.05 |
0.095
| – | – | – |
Presence of congestive heart disease | 2.14 | 1.21 to 3.79 |
0.009
| – | – | – |
Acute respiratory acidosis at admissiona | 2.41 | 1.50 to 3.88 |
< 0.001
| 2.75 (2.68) | 1.49 to 5.05 (1.34 to 5.38) |
0.001 (0.005)
|
Hypercapnia at admissionb | 1.90 | 1.26 to 2.87 |
0.002
| – | – | – |
Hypercapnia at day 3b | 2.05 | 0.97 to 4.32 |
0.061
| – | – | – |
Acute severe hypoxemia at admissioncd | 2.32 | 1.14 to 4.73 |
0.020
| |||
Renal bicarbonate retention at admissione | 1.84 | 1.21 to 2.80 |
0.004
| |||
Need for NIMV | 3.53 | 2.12 to 5.88 |
< 0.001
| |||
Pseudomonas aeruginosa in the sputum sample of the previous yearf | 4.75 | 0.96 to 23.34 |
0.055
| |||
MRCT colonisationf | 9.84 | 1.23 to 78.59 |
0.031
| |||
Pseudomonas aeruginosa in the sputum sample during hospitalisationf | 7.33 | 2.00 to 26.88 |
0.003
| |||
Streptococcus pneumoniae in the sputum sample during hospitalisationf | 0.33 | 0.11 to 0.96 |
0.042
| |||
Use of cephalosporins during hospitalisation | 4.54 | 0.98 to 21.06 |
0.053
| |||
Use of fluoroquinolones during hospitalisation | 0.61 | 0.40 to 0.93 |
0.023
|