Alterations in Respiratory Function Test Three Months after Hospitalisation for COVID-19 Pneumonia: Value of Determining Nitric Oxide Diffusion
Abstract
:1. Introduction
2. Materials and Methods
2.1. Clinical, Health, Radiographic, and Analytical Evaluation at 12 Weeks
2.2. Respiratory Function Tests at 12 Weeks
2.3. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Variables | Total N = 200 |
---|---|
Demographics and Clinics before Admission | |
Male sex, N (%), | 119 (59.5) |
Age, years | 62 (50–71) |
Body mass index (Kg/m2) | 28.7 (25.9–31.9) |
Previous and current smoker, N (%) | 84 (42) |
History of chronic cardiopathy, N (%) * | 37 (18.5) |
History of diabetes, N (%) | 23 (11.5) |
History of hypertension, N (%) | 74 (37) |
History of COPD, N (%) | 6 (3) |
History of chronic renal failure, N (%) | 7 (3.5) |
ECOG score | 1 (1–2) |
ECOG score ≥ 2, N (%) | 51 (25.5) |
In Relation to the Pneumonic Process | |
Bilateral radiographic involvement, N (%) | 139 (69.5) |
Oxygen saturation at hospital admission | 96 (94–98) |
Pneumonia Severity Index | 61 (49–75) |
Pneumonia Severity Index ≥ 3, N (%) | 62 (31) |
Need non-invasive ventilatory support, N (%) | 12 (6) |
ICU admission, N (%) | 31 (15.5) |
Lowest level of lymphocites (109/L) | 0.75 (0.55–1.04) |
Maximum level of C-reactive protein (mg/L) | 83.3 (31–160.1) |
Maximum level of LDH (U/L) | 295 (227.7–386.7) |
Maximum level of D-dimer (ng/mL) ** | 1150.1 (476.2–2856) |
Length of stay (days) | 7 (4–13) |
Spirometry | Values and Frequencies |
FVC, L | 3.62 (3.02–4.32) |
FVC, % of predicted | 103 (92.5–114.7) |
FVC < LLN, N (% (IC 95%)) | 9 (4.3 (1.5–7.1)) |
FEV1, L | 2.9 (2.43–3.45) |
FEV1, of predicted | 104 (95.2–114) |
FEV1 < LLN, N (% (IC 95%)) | 9 (4.3 (1.5–7.1)) |
FEV1/FVC (%) | 79 (75–84) |
FEV1/FVC < LLN, N (% (IC 95%)) | 9 (4.3 (1.5–7.1)) |
Post-broncodilation Changes | Values and Frequencies |
FVC, L | 0.680 (0.52–0.720) |
FVC, % | 1 (−2–5) |
FEV1, L | 0.120 (0.55–0.210) |
FEV1, % | 4 (2–8) |
Positive bronchodilator test, N (% (IC 95%)) | 13 (6.5 (3–10.1)) |
Gas Diffusion | Values and Frequencies |
DLCO, mL/min/mmHg | 21.2 (16.4–25.7) |
DLCO, % of predicted | 84 (74–97) |
DLCO < LLN, N (% (IC 95%)) | 34 (17 (11.7–22.1)) |
KCO, mL/min/mmHg/L | 4.3 (3.7–4.8) |
KCO, % of predicted | 96 (84–105) |
KCO < LLN, N (% (IC 95%)) | 13 (6.5 (3.1–9.9)) |
DLNO, mL/min/mmHg | 99.1 (73.1–115.5) |
DLNO, % of predicted | 76.5 (68.2–87.0) |
DLNO < LLN, N (% (IC 95%)) | 58 (29 (22.7–35.3)) |
KNO, mL/min/mmHg/L | 19.3 (16.6–21.6) |
KNO, % of predicted | 89.7 (83–99) |
KNO < LLN, N (% (IC 95%)) | 29 (10.5 (6.2–14.8)) |
DMCO, mL/min/mmHg | 81.5 (59–99.7) |
DMCO, % of predicted | 69 (57–80) |
DMCO < LLN, N (% (IC 95%)) | 58 (29 (22.7–35.3)) |
VC, mL | 54.3 (44–65) |
VC, % of predicted | 85 (74–97.7) |
VC < LLN (N, % (IC 95%)) | 20 (10 (5.8–14.2)) |
VA, L | 4.9 (4.2–5.7) |
VA, % of predicted | 87 (77.2–94) |
VA < LLN, N (% (IC 95%)) | 41 (20.5 (14.9–26.1)) |
DLCO < LLN N = 34 | KCO < LLN N = 13 | KNO < LLN N = 29 | VA < LLN N = 8 | DMCO < LLN N = 58 | VC < LLN N = 20 | FVC < LLN N = 9 | FEV1 < LLN N = 9 | |
---|---|---|---|---|---|---|---|---|
DLNO < LLN N = 58 | 34 (0.67) | 12 (0.26) | 17 (0.32) | 31 (0.51) | 47 (0.73) | 17 (0.34) | 6 (0.53) | 8 (0.56) |
DLCO < LLN N = 34 | 11 (0.41) | 14 (0.43) | 22 (0.49) | 30 (0.55) | 16 (0.53) | 4 (0.15) | 5 (0.18) | |
KCO < LLN N = 13 | 13 (0.74) | 9 (0.26) | 10 (0.19) | 9 (0.51) | 2 (0.16) | 3 (0.25) | ||
KNO < LLN N = 29 | 10 (0.21) | 15 (0.27) | 11 (0.49) | 2 (0.09) | 4 (0.23) | |||
VA < LLN N = 8 | 32 (0.53) | 13 (0.28) | 7 (0.25) | 7 (0.23) | ||||
DMCO < LLN N = 58 | 12 (0.19) | 5 (0.10) | 6 (0.12) | |||||
VC < LLN N = 20 | 4 (0.26) | 5 (0.32) | ||||||
FVC < LLN N = 9 | 4 (0.51) |
Variables | Total N = 200 | DLNO > LLN N = 142 | DLNO < LLN N = 58 | p |
---|---|---|---|---|
Dyspnoea According to mMRC | ||||
Dyspnoea ≥ 1, N (%) | 89 (44) | 55 (38.7) | 34 (58.6) | 0.01 |
Dyspnoea ≥ 2, N (%) | 24 (12) | 12 (8.4) | 12 (20.6) | 0.01 |
Dyspnoea | 0.0 (0–1) | 0 (0–1) | 1 (0–1) | 0.001 |
Health Status According to Nottingham Health Profile | ||||
Energy | 0 (0–33.3) | 0 (0–33.3) | 0 (0–33.3) | 0.12 |
Pain | 12.5 (0–37.5) | 12.5 (0–37.5) | 12.5 (0–62.5) | 0.15 |
Physical mobility | 12.5 (0–37.5) | 12.5 (0–37.7) | 25 (0–50) | 0.02 |
Emotional reactions | 11.1 (0–33.3) | 11.1 (0–22.2) | 11.1 (0–36.1) | 0.21 |
Sleep | 20 (0–60) | 20 (0–60) | 20 (0–80) | 0.61 |
Social isolation | 0 (0–0) | 0 (0–0) | 0 (0–20) | 0.02 |
Number of limited areas | 3 (2–4) | 3 (1–4) | 3.5 (2–5) | 0.04 |
Exercise Capacity (6MWT) | ||||
6-min walking distance, m | 457 (379.5–520.1) | 473 (416–532) | 411 (369.2–474) | 0.04 |
Initial oxygen saturation, % | 98 (97–99) | 98 (97–99) | 98 (97–98) | 0.02 |
Final oxygen saturation, % | 97 (95–98) | 97 (96–98) | 96 (94–97) | 0.001 |
Oxygen saturation drop, % | 1 (1–3) | 1 (0–2) | 2 (1–4) | 0.001 |
Borg Scale Dyspnoea Start (1–10) | 0 (0–1) | 0 (0–1) | 0 (0–1) | 0.17 |
Final Borg scale dyspnoea (1–10) | 2 (0–4) | 2 (0–4) | 1 (0–4) | 0.75 |
Laboratory Parameters | ||||
Lymphocytes x109/L | 1.8 (1.4–2.2) | 1.7 (1.4–2.2) | 1.8 (1.4–2.3) | 0.43 |
C-reactive protein, mg/L | 1.2 (0.4–3.1) | 1 (0.4–3) | 1.7 (0.5–3.1) | 0.07 |
D-dimer, ng/mL | 337 (225–565) | 317 (217–533) | 454 (263–791) | 0.02 |
Lactate dehydrogenase, U/L | 195 (173–216) | 193 (172–214) | 201 (181.2–221.5) | 0.10 |
Ferritin, ng/mL | 68 (29–136) | 74 (27–125.5) | 60 (29–145.2) | 0.98 |
NT-proBNP, pg/mL | 73 (37.7–167.2) | 74 (38.5–149.0) | 80 (34.5–204) | 0.39 |
Chest X-ray | ||||
Persistence of any lung injuries, N (%) | 52 (26) | 22 (15.5) | 30 (51.7) | 0.001 |
Variables | DLNO < LLN y DLCO > LLN N = 24 | DLNO < LLN y DLCO < LLN N = 34 | p |
---|---|---|---|
Demographics | |||
Male sex, N (%), | 20 (83.3) | 34 (100) | 0.01 |
Age, years | 60 (51–69) | 68 (61.5–74) | 0.02 |
Dyspnoea According to mMRC | |||
Dyspnoea ≥ 1, N (%) | 12 (50) | 22 (64.7) | 0.20 |
Dyspnoea ≥ 2, N (%) | 3 (12.5) | 9 (26.4) | 0.19 |
Dyspnoea | 0.5 (0–1) | 1 (0–1) | 0.06 |
Health Status According to Nottingham Health Profile | |||
Energy | 0 (0–33.3) | 0 (0–33.3) | 0.88 |
Pain | 6.2 (0–59.3) | 12.5 (0–62) | 0.51 |
Physical mobility | 31.2 (0–50) | 25 (0–50) | 0.75 |
Emotional reactions | 11.1 (0–44.4) | 11.1 (0–22.6) | 0.20 |
Sleep | 30 (0–80) | 20 (0–80) | 0.99 |
Social isolation | 0 (0–35) | 0 (0–20) | 0.19 |
Number of limited areas | 3 (2–5) | 4 (2–5) | 0.84 |
Respiratory Function Tests | |||
FVC, % of predicted | 95 (84–106.2) | 89.9 (84–97.5) | 0.16 |
FEV1, % of predicted | 94.5 (86.1–105.2) | 86.7 (80.7–99) | 0.31 |
DLCO, % of predicted | 76 (72.2–80) | 55.3 (48.5–65.5) | 0.0001 |
DLNO, % of predicted | 69 (62–70) | 51.2 (43–63) | 0.0001 |
KCO, % of predicted | 96 (84–106.2) | 76.3 (68.7–86) | 0.0001 |
KNO, % of predicted | 89 (81.2–94) | 74.4 (65–83.5) | 0.0001 |
DMCO, % of predicted | 56 (50.2–61.7)) | 42.5 (33.5–56.2) | 0.0001 |
VC, % of predicted | 81 (72.2–88.7) | 64 (33.5–56.2) | 0.0001 |
VA, % of predicted | 79 (74–87) | 72.5 (62.7–84.2) | 0.13 |
Exercise Capacity (6MWT) | |||
6-min walking distance, m | 450 (386–509) | 434 (347.5–462.7) | 0.30 |
Initial oxygen saturation, % | 98 (97–98) | 98 (97–98) | 0.67 |
Final oxygen saturation, % | 96 (95–97) | 95 (92.7–97.2) | 0.52 |
Oxygen saturation drop, % | 2 (0.2–3) | 2 (1–4.2) | 0.30 |
Borg Scale Dyspnoea Start (1–10) | 0 (0–1) | 0 (0–0) | 0.28 |
Final Borg scale dyspnoea (1–10) | 1.5 (0.2–5.5) | 1 (0–4) | 0.33 |
Laboratory Parameters | |||
Lymphocytes × 109/L | 2 (1.4–2.5) | 1.7 (1.3–2.3) | 0.42 |
C-reactive protein, mg/L | 1.7 (0.9–3) | 1.8 (0.4–5) | 0.94 |
D-dimer, ng/mL | 295 (215.2–523.7) | 510 (371.5–954.5) | 0.004 |
Lactate dehydrogenase, U/L | 204 (185–222.5) | 199 (171.5–218.7) | 0.42 |
Ferritin, ng/mL | 55 (21.2–154.2) | 83 (31.2–145.2) | 0.92 |
NT-proBNP, pg/mL | 76 (22–157.7) | 116 (52–375) | 0.16 |
Chest X-ray | |||
Persistence of any lung injuries, N (%) | 13 (53.2) | 15 (44.1) | 0.45 |
Variables | DLNO > LLN N = 142 | DLNO < LLN N = 58 | p |
---|---|---|---|
Demographics and Clinical before Admission | |||
Male sex, N (%), | 65 (45.8) | 54 (93.1) | 0.0001 |
Age, years | 61 (46.7–70) | 65,5 (56.7–73) | 0.03 |
Body mass index (Kg/m2) | 28.7 (25.4–32.3 | 28.1 (26.6–31.7) | 0.59 |
Previous and current smoker, N (%) | 47 (33.1) | 37 (63.8) | 0.001 |
History of chronic cardiopathy, N (%) | 20 (14.1) | 17 (29.3) | 0.01 |
History of diabetes, N (%) | 11 (7.7) | 12 (20.7) | 0.01 |
History of hypertension, N (%) | 47 (33.1) | 27 (46.6) | 0.07 |
History of COPD, N (%) | 1 (0.7) | 5 (8.6) | 0.003 |
History of chronic renal failure, N (%) | 3 (2.1) | 4 (6.9) | 0.11 |
ECOG score | 1 (1–1) | 1 (1–2) | 0.01 |
ECOG score ≥ 2, N (%) | 29 (20.4) | 22 (37.9) | 0.01 |
In Relation to the Pneumonic Process | |||
Bilateral radiographic involvement, N (%) | 39 (67.2) | 100 (70.4) | 0.65 |
Oxygen saturation at hospital admission | 96.5 (94–98) | 94.9 (91.5–96) | 0.0001 |
Pneumonia Severity Index | 57 (43–67.5) | 74 (62–93.5) | 0.0001 |
Pneumonia Severity Index ≥ 3, N (%) | 30 (21) | 32 (56) | 0.0001 |
Need non-invasive ventilatory support, N (%) | 5 (3.5) | 7 (12.1) | 0.02 |
ICU admission, N (%) | 14 (9.9) | 17 (29.3) | 0.001 |
Lowest level of lymphocites (109/L) | 0.82 (0.59–1.18) | 0.60 (0.42–0.81) | 0.0001 |
Maximum level of C-reactive protein (mg/L) | 62.4 (23.6–138.5) | 148.6 (88.6–217.7) | 0.0001 |
Maximum level of lactate dehydrogenase (U/L) | 277 (219.5–343.2) | 367.5 (265.2–464.2) | 0.005 |
Maximum level of D-dimer (ng/mL) * | 690.1 (423–2221.7) | 1881.5 (980–4018) | 0.001 |
Length of stay (days) | 8.8 (3–11) | 10.5 (6–26) | 0.0001 |
Authors and Reference | Lerum [1] 2020 | Shah [3] 2020 | Qin [2] 2021 | Sibila [3] 2021 | González [10] 2021 | Anastasio [8] 2021 | Belan [7] 2021 | Guler [6] 2021 | |
---|---|---|---|---|---|---|---|---|---|
Country | Norway | Canada | China | Spain | Spain | Italy | Italy | Switzerland | |
Time from hospital discharge, months | 3 | 3 | 3 | 3 | 3 | 4 | 4 | 4 | |
N | 103 | 60 | 88 | 172 | 62 | 222 | 219 | 47 Mild | 66 Severe |
Male sex, % | 52 | 68 | 42 | 57 | 74.2 | 57.2 | 59.7 | 52.9 | 60 |
Age, years | 59 | 67 | 59 | 56.1 | 60 | 58 | 61 | 57.4 | 60.3 |
BMI | 25.8 | 25 | 23.8 | - | 28.2 | 26.2 | - | 25.5 | 29.8 |
Current or previous smoking, % | 36 | 38 | - | 27.3 | 56.7 | 37.9 | 41.1 | 37 | 56 |
ICU admission, % | 15 | - | - | 43 | 100 | 15.3 | 11.8 | - | |
Length of stay (days) | 6 | 10 | - | - | - | - | |||
Diabetes, % | 8 | 22 | 9 | 14.5 | 14.5 | 9.5 | 15.1 | 0 | 35 |
COPD or asthma % | - | 13 | - | 11.6 | 9.6 | 9.1 | 5.8 | 22 | 21 |
Hypertension, % | 35 | 35 | 28 | 33.1 | 37.1 | 39.6 | 41.2 | 8 | 55 |
Cardiopathy, % | - | 10 | 9 | 13.9 | 9.4 | 15.3 | 16.3 | 9 | 10 |
Dyspnoea mMRC > 0 | 54 | 20 | 48.8 | 46.7 | 48.2 | 5.5 | - | - | |
Dyspnoea mMRC > 1 | - | - | - | - | 20.7 | - | - | - | |
Chest CT | Yes | Yes | - | No | Yes | No | No | Yes | |
FVC, % | 94 | 94 | 89.7 | 90 | 81.5 | 105 | 98.5 | 95.6 | 86.6 |
FEV1, % | 92 | 93 | 92.9 | 94 | 88.9 | 106 | 101 | 94 | 89.4 |
DLCO, % | 83 | 77 | 82-6 | - | - | - | 79 | 95.3 | 72.2 |
DLCO < LLN, % | 24 | - | - | - | - | - | - | - | - |
DLCO < 80%, % | - | 52 | 54 | 57 | 82 | - | 51.6 | - | - |
DLCO/VA, % | 95 | - | 86.1 | - | - | 101 | - | - | - |
DLCO/VA < 80% | 38 | - | . | ||||||
6-min walking distance, m | 580 | 504 | - | - | 400 | 500 | - | 576 | 456 |
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Núñez-Fernández, M.; Ramos-Hernández, C.; García-Río, F.; Torres-Durán, M.; Nodar-Germiñas, A.; Tilve-Gómez, A.; Rodríguez-Fernández, P.; Valverde-Pérez, D.; Ruano-Raviña, A.; Fernández-Villar, A. Alterations in Respiratory Function Test Three Months after Hospitalisation for COVID-19 Pneumonia: Value of Determining Nitric Oxide Diffusion. J. Clin. Med. 2021, 10, 2119. https://doi.org/10.3390/jcm10102119
Núñez-Fernández M, Ramos-Hernández C, García-Río F, Torres-Durán M, Nodar-Germiñas A, Tilve-Gómez A, Rodríguez-Fernández P, Valverde-Pérez D, Ruano-Raviña A, Fernández-Villar A. Alterations in Respiratory Function Test Three Months after Hospitalisation for COVID-19 Pneumonia: Value of Determining Nitric Oxide Diffusion. Journal of Clinical Medicine. 2021; 10(10):2119. https://doi.org/10.3390/jcm10102119
Chicago/Turabian StyleNúñez-Fernández, Marta, Cristina Ramos-Hernández, Francisco García-Río, María Torres-Durán, Andrés Nodar-Germiñas, Amara Tilve-Gómez, Paula Rodríguez-Fernández, Diana Valverde-Pérez, Alberto Ruano-Raviña, and Alberto Fernández-Villar. 2021. "Alterations in Respiratory Function Test Three Months after Hospitalisation for COVID-19 Pneumonia: Value of Determining Nitric Oxide Diffusion" Journal of Clinical Medicine 10, no. 10: 2119. https://doi.org/10.3390/jcm10102119