Table 3.
Clinical conditions of pulmonary hypoxia in which derangement of the ADMA / DDAH pathway was described.
| Clinical condition | Study design | Functional consequence | References |
|---|---|---|---|
| High altitude | |||
| Chronic-intermittent hypobaric hypoxia | 72 healthy Chilean lowlanders exposed to CIH during 3 months; 16 Andean highlander natives | ADMA ↑ by 80 % in CIH; no change in SDMA in CIH; highest ADMA in highland natives | (153) |
| Chronic-intermittent hypobaric hypoxia | 100 healthy Chilean lowlanders exposed to CIH during 6 months; echocardiography at 6 months | ADMA ↑ in CIH; SDMA ↓ in CIH; individuals with highest ADMA had highest risk of HAPH | (60) |
| Chronic intermittent hypobaric hypoxia | 120 Chilean mining workers after exposure to CIH for a mean 14 ± 0.5 years | ADMA, but not SDMA, ↑ as compared to reference levels; higher ADMA in workers with HAPH (mPAP > 30 mm Hg) than in those without | (24) |
| High altitude pulmonary oedema | 200 HAPE patients, 200 HAPE-free altitude sojourners, and 450 healthy highlanders | ADMA significantly ↑ in HAPE-patients and in highlanders than in HAPE-free sojourners | (154) |
| Acute hypobaric hypoxia (hypobaric chamber) | 12 healthy humans during a 24 h stay in a hypobaric chamber |
N = 5 developed AMS, high mPAP, and decreased ADMA; N = 4 had mild AMS, mildly elevated mPAP, and elevated ADMA |
(155) |
| Obstructive sleep apnea syndrome | |||
| Obstructive sleep apnea syndrome | 188 OSAS patients, 520 controls | No difference in ADMA between OSAS and controls | (156) |
| Obesity | 518 obese individuals; 242 OSAS patients, 276 non-OSAS individuals | ADMA and SDMA ↑ with increasing AHI | (157) |
| Obstructive sleep apnea syndrome | 95 patients with suspected OSAS undergoing polysomnography | Significant inverse linear correlation between AHI and flow-mediated vasodilation in the forearm; ADMA significantly ↓ after 3 months of CPAP therapy in 63 OSAS patients with AHI>20 |
(158) |
| Obstructive sleep apnea syndrome | 40 OSAS patients 20 healthy controls |
ADMA ↑ in OSAS vs. controls | (159) |
| Obstructive sleep apnea syndrome | 13 patients with severe OSAS, 13 patients with mild-to-moderate OSAS, 12 controls |
ADMA not significantly higher in severe or mild-to-moderate OSAS than in controls; ADMA significantly correlated to arousal index | (160) |
| Obstructive sleep apnea syndrome | OSAS patients with (N = 23) or without (N = 18) concomitant CV risk factors, 23 healthy controls | ADMA ↑ in OSAS, but not related to the presence of CV risk factors | (161) |
| Obstructive sleep apnea syndrome | 34 OSAS patients, 15 healthy controls |
ADMA ↑ and NO metabolite levels ↓ in OSAS | (162) |
| Children with OSAS | 26 children with OSAS, 8 healthy controls |
No significant difference in ADMA between OSAS and control children | (163) |
| Obstructive sleep apnea syndrome | 10 male OSAS patients before and after CPCP therapy | Significant improvement in flow-mediated vasodilation after CPAP therapy, concomitant with ↓ ADMA | (164) |
| Chronic obstructive lung disease | |||
| COPD | 29 stable COPD, 35 exacerbated COPD, 15 control smokers | Serum L-arginine/ADMA ratio ↓ in stable and exacerbated COPD; serum SDMA ↑ in COPD and decreased after systemic steroid treatment | (165) |
| COPD | COPD patients with or without PAH (sPAP > 35 mm Hg), healthy controls | ADMA ↑ in COPD with PAH vs. both other groups | (166) |
| COPD | 42 patients with mild to very severe COPD, with or without PAH (sPAP > 36 mm Hg) | ADMA and SDMA ↑ with decreasing FEV1, but SDMA ↓again with very low FEV1; ADMA and SDMA slightly, but not significantly higher in COPD patients with PAH | (167) |
| COPD | 74 COPD patients | Significant correlation of ADMA with airway resistance in patients with poorly controlled airway obstruction; ADMA significantly associated with airway resistance in multiple linear regression (R = 0.42 [0.06–0.77]) | (168) |
| Stable COPD | 60 patients with stable COPD, 20 smoking and 20 non-smoking healthy controls | Brachial artery intima-media thickness (IMT) ↑ in COPD than in controls; significant correlation of IMT with ADMA | (169) |
| Exacerbated COPD | 150 patients with acute exacerbation of COPD; 6 years of prospective follow-up for total mortality | ADMA and SDMA ↑ in more severe pneumonia and with higher SOFA Score; highest quartiles of ADMA and SDMA significantly associated with all-cause mortality (54%) after 6 years | (170) |
| Elderly patients with stable COPD | 41 COPD patients, 35 elderly controls | Bronchial obstruction (FEV1) associated with arterial stiffness and brachial artery flow-mediated vasodilation; no correlation with ADMA | (171) |
| COPD | 58 COPD patients, 30 healthy controls | ADMA ↑ in COPD, whilst serum NOx ↓ in COPD—inverse correlation between both parameters; ADMA inversely correlated with FEV1, ADMA ↑ with progression of COPD stage | (172) |
| Stable and exacerbated COPD | 32 patients with stable COPD, 12 patients with acute exacerbation of COPD, 30 healthy controls | ADMA and SDMA ↑ in COPD than controls; ADMA and SDMA ↑ in exacerbated vs. stable COPD | (173) |
| Mild to moderate COPD | 43 COPD patients, 43 matched controls | Non-significant increase in ADMA in mild and moderate COPD; ADMA/arginine ratio associated with COPD severity | (174) |
| COPD | 10 COPD patients | Sputum ADMA correlates with sputum L-ornithine and L-citrulline | (175) |
| Overlap syndrome | |||
| COPD patients, OSAS patients, and patients with overlap syndrome (OS) | 26 patients with COPD, 25 with OSAS, and 24 with OS | ADMA ↑ in COPD vs. OSAS or OS; no change in ADMA after 30 days of CPAP treatment in OSAS and OS patients | (176) |
| COPD patients, OSAS patients, and patients with overlap syndrome (OS) | 25 patients each with COPD, OSAS, or OS | ADMA ↑ in COPD vs. OSAS or overlap syndrome; no change in ADMA after 4 weeks of CPAP treatment in OS | (177) |
| Pulmonary arterial hypertension | |||
| Idiopathic PAH | Patients with IPAH, healthy controls | ADMA ↑ in IPAH vs. healthy controls; significant association of ADMA with right ventricular function and with mortality | (178) |
| PAH in systemic sclerosis | 66 European patients with systemic sclerosis (24 with PAH, 42 without PAH), 30 age-matched healthy controls | ADMA ↑ in systemic sclerosis with PAH, not in systemic sclerosis without PAH | (179) |
| PAH in connective tissue disease | 88 Chinese patients with connective tissue diseases (43 with PAH, 45 without PAH), and 40 healthy controls |
ADMA ↑ in connective tissue diseases with PAH, not in connective tissue diseases without PAH | (180) |
| HIV-associated PAH | 214 HIV patients, of whom 85 underwent right heart catheterization for suspected PAH | ADMA ↑ in HIV patients with PAH than in those without; mPAP 14.2% higher per each 0.1 μmol/L increase in ADMA | (181) |
| CTEPH | 135 CTEPH patients, 40 healthy controls | ADMA ↑ in CTEPH patients than in controls | (182) |
| COVID-19 | |||
| Patients hospitalized with severe COVID-19 | 31 patients hospitalized with severe COVID-19 | ADMA and SDMA ↑ in COVID-19 non-survivors than in survivors; ADMA and SDMA were best predictors of in-hospital mortality of COVID-19 patients | (71) |
AMS, acute mountain sickness; CIH, chronic intermittent hypoxia; COPD, chronic obstructive lung disease; CTEPH, chronic thromboembolic pulmonary hypertension; HAPE, high altitude pulmonary edema; HAPH, high altitude pulmonary hypertension; HIV, human immunodeficiency virus; iPAH, idiopathic pulmonary arterial hypertension; mPAP, mean pulmonary arterial pressure; OSAS, obstructive sleep apnea syndrome; PAH, pulmonary arterial hypertension; sPAP, systolic pulmonary arterial pressure.