Lung Surfactant Proteins A (SP-A) and D (SP-D) in Chronic Obstructive Pulmonary Disease (COPD)
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Introduction: The biomarkers used in COPD are many, but studies of last decades are focused on the pulmonary surfactant, which plays a crucial role in normal lung function. Aim : Evaluation of the levels of SP-A, SP-D and other markers in patients with SPOK and their relation to inflammation and smoking. Material : We studied 118 patients with COPD . 10 cases were in stage B, 24 cases in stage C and 84 cases in stage D; 113 males and 5 females , mean age 69 ± 8 years and 70 ± 8 years respectively; Methodology: The SP-A and SP-D levels were measured on admission during acute exacerbation and in the day of discharge from hospital in remission of disease. We included a healthy control group. Results: In the healthy control group mean SP-A = 22.2 +/- 16.3 ng / ml and mean SP-D=90 +/- 36.8 ng / ml . In our study group ,on admission we found mean SP-A levels 46.8 + -35.2ng / ml and SP-D 175 +/- 99 ng / ml. In COPD Stage B mean SP-A was 33.78 +/- 19.7 ng / ml, Stage C 40.7 +/- 19.5ng / ml and stage D 50.2 +/- 39 ng / ml (p = 0.0001). Mean SP-D at Stage B was 168.3 +/- 121ng / ml, Stage C 160 +/- 78 ng / ml, and Stage D 181 +/- 102ng / ml (p = 0.0001).On the last day(remission) mean SP-A 38+ /23.5ng/ml and mean SP-D 147 +/- 91 ng / ml. In COPD Stage B mean SP-A was 42.7 +/- 26.2 ng / ml, Stage C 33 +/- 15.6ng / ml and stage D 38.5 +/- 25 ng / ml (p = 0.003). Mean SP-D at Stage B was 196 +/- 157ng / ml, Stage C 130 +/- 53 ng / ml, and Stage D 137 +/- 81ng / ml (p = 0.002). In exacerbation period smoking status has significant correlations with all biomarkers presented with the Spearman coefficient: SP-A( R s = 0.249, p = 0.002); SP-D( R s = 0.264 p = 0.001), IL6( R s = 0.255, p = 0.002) and CRP ( R s = 0.231, p = 0.004). In remission state smoking has significant positive correlation with SP-D (R s = 0.282, p = 0.002) and SP-A (R s = 0.273, p = 0.003) .In both evaluations the mean values of SP-A and SP-D were significantly higher in smokers compared to nonsmokers (p<0.05). Levels of IL6 measured in first day were significantly higher in smokers p=0.025, mean CRP levels had no significant diffierencies between two groups. Conclusion: SP-A and SP-D levels were higher in COPD patients compared to healthy control group. Their level were significantly higher AECOPD than in stable state of COPD and they correlated with the gravity of the disease. In remission state SP-A and SP-D levels reflects better the gravity of COPD. SP-A and SP-D levels are better related with smoking state and their levels are more increased in smokers . Keywords: COPD, acute exacerbation of COPD (AECOPD), SP-A and SP-DKeywords:
Group B
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Abstract Background The serum surfactant protein D (SP-D) level is suggested to be a useful biomarker for acute lung injuries and acute respiratory distress syndrome. Whether the serum SP-D level could identify the severity of coronavirus disease 2019 (COVID-19) in the early stage has not been elucidated. Methods We performed an observational study on 39 laboratory-confirmed COVID-19 patients from The Fourth People’s Hospital of Yiyang, Hunan, China. Receiver operating characteristic (ROC) curve analysis, correlation analysis, and multivariate logistic regression model analysis were performed. Results In the acute phase, the serum levels of SP-D were elevated significantly in severe COVID-19 patients than in mild cases (mean value ± standard deviation (SD), 449.7 ± 125.8 vs 245.9 ± 90.0 ng/mL, P <0.001), while the serum levels of SP-D in the recovery period were decreased dramatically than that in the acute phase (mean value ± SD, 129.5 ± 51.7 vs 292.9 ± 130.7 ng/ml, P <0.001), and so were for the stratified patients. The chest CT imaging scores were considerably higher in the severe group compared with those in the mild group (median value, 10.0 vs 9.0, P = 0.011), while markedly lower in the recovery period than those in the acute phase (median value, 2.0 vs 9.0, P <0.001), and so were for the stratified patients. ROC curve analysis revealed that areas under the curve of lymphocyte counts (LYM), C-reaction protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), and SP-D for severe COVID-19 were 0.719, 0.833, 0.817, 0.837, and 0.922, respectively. Correlation analysis showed that the SP-D levels were negatively correlated with LYM (r = − 0.320, P = 0.047), while positively correlated with CRP (r = 0.658, P <0.001), IL-6 (r = 0.471, P = 0.002), the duration of nucleic acid of throat swab turning negative (r = 0.668, P <0.001), chest CT imaging score on admission (r = 0.695, P <0.001) and length of stay (r = 0.420, P = 0.008). Multivariate logistic regression model analysis showed that age ( P = 0.041, OR = 1.093) and SP-D ( P = 0.008, OR = 1.018) were risk factors for severe COVID-19. Conclusions Elevated serum SP-D level was a potential biomarker for the severity of COVID-19; this may be useful in identifying patients whose condition worsens at an early stage.
Erythrocyte sedimentation rate
Surfactant protein D
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Objective To investigate the dynamic changes of lung surfactant protein D( SP- D) in serum and bronchoalveolar lavage fluid( BALF) in patients with acute respiratory distress syndrome( ARDS) and to examine its clinical significance. Methods A total of 79 patients with ARDS treated in Zhejiang Provincial People's Hospital ICU between December2008 and December 2013 were included in this study. We divided the patients into two groups: the survival group( n = 56) and the death group( n = 23). Another 20 healthy adults who received physical examination in Zhejiang Provincial People's Hospital between January 2011 and December 2013 were enrolled as the control group. We sampled 2 ml of venous blood and 2 ml of BALF from each subject of the survival group and the death group on day 1( D1),day 3( D2),day 5( D3) and day 7( D4) after their diagnosis. We also sampled 2 ml of venous blood and 2 ml of BALF from each subject of the control group on each of the four days. The SP- D levels of serum and BALF of the three groups were tested and compared. Results( 1) The SP- D levels of serum were significantly different( Ftotal= 73. 26,P 0. 05) at different time points among the three groups. The SP- D levels of serum were significantly different( Finter- group= 197. 01,P 0. 05) among the three groups. The SP- D levels of serum were also significantly different( Ftime points= 168. 29, P 0. 05) at different time points.( 2) The SP- D levels of BALF were significantly different( Ftotal= 98. 71,P 0. 05) at different time points among the three groups. The SP- D levels of BALF were significantly different( Finter- group= 376. 91,P 0. 05) among the three groups. The SP- D levels of BALF were also significantly different( Ftime points= 125. 08,P 0. 05) at different time points. Conclusion The SP- D level of serum in the subjects with ARDS began to rise higher than the control group,with the death group rising higher than the survival group; the SP- D level of serum in the survival group began to decrease on day 7,while that in the death group continued to rise. The SP- D level of BALF in the subjects with ARDS was higher than the control group from the early stage after diagnosis; the SP- D level of BALF in the survival group began to decrease on day 5,while the death group continued to increase and began to decrease on day 7. The research of dynamic changes of SP- D level in serum and BALF was of guiding significance in clinical diagnosis and treatment and prognosis judgment for patients with ARDS.
Venous blood
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Objective
To determine the levels and significance of Krebs von den lungen-6 (KL-6) , pulmonary surfactant protein A (SP-A), SP-D and interleukin (IL)-6 in patients with connective tissue disease interstitial lung disease (CTD-ILD).
Methods
The serum KL-6, SP-A, SP-D and IL-6 in all subjects were detected and the imaging and pulmonary function were recorded t test, χ2 test, non-parametric test, ANOVA and correlation analysis were used for data analysis.
Results
① The levels of serum KL-6, SP-A, SP-D, IL-6 in the CTD-ILD group [551.4(428.2, 883.5) U/ml, 938.4 (435.2, 2324.7) pg/ml, 90.7(80.7, 100.3) ng/ml and 30.4 (22.9, 41.7) pg/ml; P all<0.05] was significantly higher than that in the CTD group [192.9(139.2, 266.2) U/ml; 458.0 (372.6, 529.0) pg/ml; 80.0(71.2, 98.3) ng/ml; 18.6(4.9, 31.0) pg/ml, Z=-5.383, -3.76, -2.123,-3.903, P all <0.05]; and higher than healthy controls (n=30) [183.2(141.9, 216.6) U/ml; 229.0(162.0, 248.0) pg/ml; 50.8(26.1, 96.4) ng/ml; 7.1(3.7, 8.7) pg/ml, Z=-5.801, -8.13, 2.272, 3.266; P all<0.05]. ② The levels of KL-6 in pulmonary HRCT for active ILD group was significantly higher than the non-active ILD group [998.5(640.3, 1293.3) U/ml vs 565.0(434.0, 799.5) U/ml, Z=2.182, P=0.023], there was no statistical difference in the levels of SP-A, SP-D, IL-6 between the 2 groups. ③ Spearman correlation analysis showed that KL-6 was negatively correlated with forced vital capacity (FVC%); SP-D, IL-6 and diffusing capacity of carbon monoxide (DLCO%). ④ Logistic multiple regression analysis showed that KL-6 [OR=1.017, P=0.002, 95%CI(1.006, 1.028)], SP-A [OR=1.023, P=0.009, 95%CI(1.006, 1.041)], SP-D[OR=1.175, P=0.009, 95%CI(1.075, 1.264)], IL-6[OR=1.213, P=0.001, 95%CI(1.088, 1.354)] were the risk factors for ILD.
Conclusion
Serum KL-6, SP-A, SP-D and IL-6 are significantly increased and correlate with CTD-ILD. KL-6 is related to the pulmonary inflammatory disease and vital capacity, while SP-D and IL-6 are related to diffusion function.
Key words:
Connective tissue diseases; Lung diseases, interstitial; Pulmonary surfactant-associated proteins; Krebs von den lungen-6
Surfactant protein D
CTD
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To research the soluble CD8 molecules (sCD8) levels in serum and sputum in COPD patients with exacerbation. Methods: We examined 61 patients 44-69 years old (62 ± 4.8) with COPD I (n = 21), COPD II (n = 22) and stage III (n = 27) and 30 healthy non-smokers. The concentration of soluble CD8 molecules was measured using the immunoassay method (U/ml). Results: sCD8 levels in serum were significantly increased in COPD I (775.1±105.2 U/ml, р=0.04) and COPD II patients (684.1±47.1 U/ml, р=0.005) compared to non-smokers (482.8±35.6 U/ml). Serum concentration of sCD8 in patients with stage III (502.1±35.8 U/ml) was lower by 1.54 times (p=0.015) compared to the values of COPD I and 1.4 times (p=0.003) than COPD II and did not differ from the control group. The content of sCD8 in induced sputum in patients with stage I and II disease had no a significant difference compared to the healthy non-smokers (434.4±53.2 U/ml). A statistically significant decrease in the level of studied molecules as relative to control and compared to less severe forms of the disease was detected in severe COPD (280.7±20.3 U/ml, p<0.05). There were a positive correlation between the lung function parameter FEV1, FEV1/FVC and concentration of sCD8 in serum (r=0.4 p=0.01, r=0.43 p=0.002), in sputum (r=0.5 p=0.01, r=0.53 p=0.01). Conclusion: Thus, progressing of bronchial obstruction in patients with COPD is associated with the decrease in sCD8 concentration both on the system, and at the topical level. We may consider concentrations of these molecules as additional systemic and local markers of airflow obstruction degree and disease severity.
Copd exacerbation
Pathophysiology
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Background: Osteopontin (Opn) is recognized as an important adhesive bone matrix protein and a key cytokine involved in immune cell recruitment and tissue repair and remolding.However, serum levels of osteopontin have not been evaluated in patients with chronic obstructive pulmonary disease (COPD).Thus, the aim of this study was to evaluate and compare the serum levels of osteopontin in patients experiencing COPD exacerbations and in patients with stable COPD.Methods: Serum samples were obtained from 22 healthy control subjects, 18 stable COPD patients, and 15 COPD with exacerbation patients.Serum concentrations of osteopontin were measured by the ELISA method.Results: Serum levels of osteopontin were higher in patients with acute exacerbation than with stable COPD and in healthy control subjects (62.4±51.9ng/mL, 36.9±11.1 ng/mL, 30±11 ng/mL, test for trend p=0.003).In the patients with COPD exacerbation, the osteopontin levels when the patient was discharged from the hospital tended to decrease compared to those at admission (45±52.1 ng/mL, 62.4±51.9ng/mL, p=0.160).Osteopontin levels significantly increased according to patient factors, including never-smoker, ex-smoker and current smoker (23±5.7 ng/mL, 35.5±17.6 ng/mL, 58.6±47.8ng/mL, test for trend p=0.006).Also, osteopontin levels showed a significantly negative correlation with forced expiratory volume in one second (FEV 1 %) predicted in healthy controls and stable COPD patients (r=-0.389;p=0.013).C-reactive protein (CRP) was positively correlated with osteopontin levels in patients with COPD exacerbation (r=0.775;p=0.002). Conclusion:The serum levels of osteopontin increased in patients with COPD exacerbation and tended to decrease after clinical improvement.These results suggest the possible role of osteopontin as a biomarker of acute exacerbation of COPD.
Osteopontin
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The present study examined the relationship between polymerase chain reaction (PCR) test positivity and clinical outcomes of vitamin D levels measured within the 6 months before the PCR test in coronavirus disease 2019 (COVID-19)-positive patients. In this retrospective cohort study, COVID-19 (227) and non-COVID-19 patients (260) were divided into four groups according to their vitamin D levels: Group I (0-10 ng/ml), Group II (10-20 ng/ml), Group III (20-30 ng/ml), and Group IV (vitamin D > 30 ng/ml). Laboratory test results and the radiological findings were evaluated. In addition, for comparative purposes, medical records of 1200 patients who had a hospital visit in the November 1, 2019-November 1, 2020 period for complaints due to reasons not related to COVID-19 were investigated for the availability of vitamin D measurements. This search yielded 260 patients with tested vitamin D levels. Vitamin D levels were below 30 ng/ml in 94.27% of 227 COVID-19-positive patients (average age, 46.32 ± 1.24 years [range, 20-80 years] and 56.54% women) while 93.07% of 260 non-COVID-19 patients (average age, 44.63 ± 1.30 years [range, 18-75 years] and 59.50% women) had vitamin D levels below 30 ng/ml. Nevertheless, very severe vitamin D deficiency (<10 ng/ml) was considerably more common in COVID-19 patients (44%) (average age, 44.15 ± 1.89 years [range, 23-80 years] and 57.57% women) than in non-COVID-19 ones (31%) (average age, 46.50 ± 2.21 years [range, 20-75 years] and 62.5% women). Among COVID-19-positive patients, the group with vitamin D levels of >30 ng/ml had significantly lower D-dimer and C-reactive protein (CRP) levels, number levels, number of affected lung segments and shorter hospital stays. No difference was found among the groups in terms of age and gender distribution. Elevated vitamin D levels could decrease COVID-19 PCR positivity, D-dime and CRP levels and the number of affected lung segments in COVID-19-positive patients, thereby shortening the duration of hospital stays and alleviating the intensity of COVID-19.
Medical record
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To study the variation and clinical significance of serum levels of surfactant proteins A (SP-A) and D (SP-D) among children with different degrees of bronchiolitis.Seventy children with bronchiolitis were divided into acute (n=42) and recovery phase groups (n=28). According to the severity of symptoms, the acute phase group was further divided into severe (n=12) and mild subgroups (n=30). Another 26 children who were hospitalized in the same period due to non-infectious diseases and had not undergone surgery were used as the control group. Competitive enzyme-linked immunosorbent assay was performed to measure serum levels of SP-A and SP-D in each group.The acute phase group had significantly higher serum levels of SP-A and SP-D compared with the recovery phase (P<0.01) and control groups (P<0.01). Compared with the control group, the recovery phase group had elevated levels of SP-A and SP-D (P<0.01). Within the acute phase group, serum levels of SP-A and SP-D in the severe subgroup were significantly higher than in the mild subgroup (P<0.01).Serum levels of SP-A and SP-D are significantly elevated in children with acute bronchiolitis, and severe cases have higher serum levels of SP-A and SP-D than mild cases. Even after the relief of clinical symptoms, serum levels of SP-A and SP-D remain high. These findings suggest that serum levels of SP-A and SP-D might be useful biomarkers for evaluating the severity of bronchiolitis among children.
Acute Bronchiolitis
Clinical Significance
Surfactant protein D
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Objective
To analyze the alterations and clinical significance of serum calcium binding protein S100A8/A9 and soluble receptor for advanced glycation end products (sRAGE) levels in patients with chronic obstructive pulmonary disease(COPD).
Methods
Enzyme-linked immonosorbent assay was established to detect serum levels of S100A8/A9 and sRAGE in 203 patients with COPD[male166, female 37, aged 52-92 years, average years(69.72±9.079)] and in 41 smoking elderly non-COPD patients[male 35,female 6, aged 55-89 years, average years(68.66±8.74)], and 167 non-smoking healthy subjects as the control group[male 132, female 35, aged 57-92 years, average years(69.13±7.21)] from April 2018 to January 2019. The relationship between the S100A8/A9, sRAGE and clinical biomarkers [the percentage of fored expiratory volume in one second(FEV1) in the predicted value, FEV1/fored vital capacity(FVC), neutrophile granulocyte(NEU)%, pack-year] were investigated. The diagnostic value of S100A8/A9, sRAGE and their combined detection for COPD was analyzed using the subject operating characteristic curve.
Results
The serum S100A8/A9 level [(2.70±1.11)μg/ml] in COPD patients was significantly higher than that in the smoking control group [(1.65±0.63) μg/ml] and the non-smoking control group[(0.99±0.48)μg/ml], t=5.807, P<0.000 1; t=18.45, P<0.000 1. The serum S100A8/A9 levels in patients with COPD[GOLD Ⅰ(2.08±1.08) μg/ml, GOLDⅡ (2.58±1.06) μg/ml, GOLD Ⅲ (2.69±1.12) μg/ml, GOLDⅣ (2.95±1.10)μg/ml] were significantly higher than the non-smoking control group(0.99±0.48)μg/ml, t=6.616, P<0.000 1; t=14.56, P<0.000 1; t=17.10, P<0.000 1; t=18.09, P<0.000 1.The serum sRAGE level [(0.29±0.25)ng/ml] in COPD patients was significantly higher than that in the smoking control group[(0.60±0.24)ng/ml] and the non-smoking control group[(0.85±0.35)ng/ml], t=7.367, P<0.000 1; t=18.14, P<0.000 1. The serum sRAGE levels in patients with COPD[GOLD Ⅰ(0.46±0.40),GOLDⅡ (0.28±0.25),GOLD Ⅲ (0.29±0.25),GOLD Ⅳ (0.25±0.19)ng/ml] were significantly lower compared with non-smoking control group[(0.85±0.35)ng/ml], t=3.459, P=0.000 5; t=10.23, P<0.000 1; t=13.95, P<0.000 1; t=11.70, P<0.000 1. Serum S100A8/A9 levels were positively correlated with smoking amount and NEU% (r=0.458 5, P<0.000 1; r=0.228 3, P=0.001 1), negatively correlated with FEV1/FVC, the percentage of FEV1 in the predicted value, and sRAGE(r=-0.190 6, P=0.006 4; r=-0.186 3, P=0.007 8; r=-0.201 7, P=0.003 9). sRAGE levels were negatively correlated with NEU% (r=-0.155 9, P=0.026 4). In the ROC curve, the area under the curve of S100A8/A9, sRAGE and combined detection were 0.922[95%CI(0.897-0.947)], 0.926[95%CI(0.899-0.952)]and 0.966 [95%CI(0.950-0.983)], respectively.
Conclusion
S100A8/A9 and sRAGE are closely correlated with the degree of airflow constrains and the levels of serum inflammatory mediators, which are expected to be as potential biomarkers of COPD.
Key words:
Pulmonary disease, chronic obstructive; Calgranulin A; Calgranulin B; Receptor for advanced glycation end products
S100A8
Clinical Significance
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Objective
To investigate the changes of serum C reactive protein (CRP), D-two polymer (D-D) and calcitonin (PCT) in patients with severe chronic obstructive pulmonary disease (COPD) and its clinical value.
Methods
A retrospective analysis was conducted in 146 patients with severe COPD at acute attack in Tongji Huangzhou Hospital of Huazhong University of Science and Technology from December 2015 to December 2017.In addition, 146 cases of COPD at remission stage (remission group) and 80 healthy subjects (control group) who were admitted to the hospital during the same period were selected.The serum levels of D-D, hs-CRP and PCT were compared among the three groups.At the same time, the levels of serum D-D, hs-CRP and PCT in patients with no bacterial infection or different pulmonary function classification were compared.
Results
The serum levels of D-D, hs-CRP and PCT in the acute group[(1 927.4±83.4)μg/L, (39.3±3.2)mg/L, (5.8±1.7)ng/mL] were significantly higher than those in the remission group[(314.2±69.2)μg/L, (16.4±3.4)mg/L, (1.8±0.7)ng/mL], which in the remission group were also significantly higher than the control group[(231.7±58.5)μg/L, (3.8±1.5)mg/L, (0.4±0.1)ng/mL], the differences were statistically significant (F=35.487, 11.266, 6.752, P=0.001, 0.005, 0.000). The serum levels of hs-CRP and PCT in the acute phase combined with bacterial infection group[(41.4±1.7)mg/L, (6.4±1.4)ng/mL] were higher than those in the non bacterial infection group [(36.3±1.2)mg/L, (5.0±1.0)ng/mL](F=16.541, 4.467, P=0.000, 0.011), but there was no statistically significant difference in D-D level (P>0.05). There were statistically significant differences in serum D-D, hs-CRP and PCT levels among patients with different pulmonary function classification [serum D-D: (2 083.5±88.3)μg/L vs.(1 727.3±71.3)μg/L vs.(1 523.5±67.3)μg/L; hs-CRP: (63.8±19.5)mg/L vs.(29.5±10.4)mg/L vs.(10.6±3.2)mg/L; PCT: (6.2±1.3)ng/mL vs.(3.4±0.9)ng/mL vs.(1.3±0.4)ng/mL] (F=34.493, 15.488, 6.567, P=0.000, 0.001, 0.018), and the higher the pulmonary function classification, the higher the above indicators(all P<0.05).
Conclusion
The levels of serum CRP, D-D and PCT in patients with severe COPD at acute attack are significantly increased, and the increase of the patients with bacterial infection is more obvious, and the index level is positively correlated with the classification of lung function, which can provide a reference for clinical practice.
Key words:
Pulmonary disease, chronic obstructive; C-reactive protein; Calcitonin; D-two polymer
Procalcitonin
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Background: Surfactant protein A (SP-A) serum levels is known to be increased in pulmonary alveolar proteinosis (PAP),a disorder characterized by alveolar accumulation of surfactant lipoprpoteins. The prognostic value of SP-A in PAP is still unknown and has been investigated in our study. Patients and methods : 28 consecutive patients with PAP were studied prospectively. Serum SP-A was measured by ELISA.We evaluated the correlation between initial SP-A levels, clinical variables and other serum biomarkers. Disease progression was defined as deterioration of symptoms, lung function or chest imaging. Results : The median follow-up time was 510 (90-1890) days. Initial serum SP-A levels correlated inversely with baseline PaO2, FVC und TLCO (r=-0.405, p=0.004; r=-0.46, p=0.001 und r=- 0.462, p=0.003) and directly with AaO2 (r=0.315, p=0.026). Serum SP-A also correlated with LDH (r=0.451, p=0.001) and KL-6 (r=0.363, p=0.008). A correlation between changes in TLCO, PaO2 and AaO2 and changes in serum SP-A during the follow-up was seen (r=-0.7, p=0.002; r=-0.538, p=0.007; r=0.436, p=0.033 respectively). Serum SP-A was higher in patients with disease progression (n=14) (p=0.001). At a cut-off level of 490 ng/mL, serum SP-A predicted disease progression with a sensitivity of 88% and specificity of 75% and the necessity of whole lung lavage (WLL) with a sensitivity of 86% and specificity of 70%. In the multivariate analysis, the initial serum SP-A level was an independent predictor of disease progression (HR 3.9, p=0.046) and of the necessity of WLL (HR 7.2, p=0.003). Conclusions : Serum SP-A appears to have a predictive value for disease progression in PAP.
DLCO
Pulmonary alveolar proteinosis
Surfactant protein D
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