Clinical Analysis Of 49 Patients With Pulmonary Alveolar Proteinosis

Background:Pulmonary alveolar proteinosis (PAP) is an uncommon disease caused by accumulation of surfactant components in the distal airways and alveoli. Patients suffer progressive dyspnea and hypoxemia with airway obstruction and impaired diffuse capacity. The histopathology of lung tissue and bronchoalveolar lavage fluid reveals periodic acid-Schiff stain (PAS) positive. The onset of PAP is usually insidious and the clinical presentations are non-specific, often causing misdiagnosis and missed diagnosis and the prognosis remains uncertain. Several reports have found several serum markers elevated in PAP, but the significance remains unclear. To improve the understanding of PAP, we described clinic features of PAP patients and effect of lung lavage, explored the relation between serum markers and disease severity.Methods:Clinical data including lung function, chest high resolution CT(HRCT), and laboratory examinations (arterial blood gas analysis, blood biochemical examination and serum tumor markers) were collected from 49 PAP patients diagnosed in second Affiliated Hospital of Zhejiang University School of Medicine, Sir Run Run Shaw Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang Provincial People’s Hospital, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou Hospital of Traditional Chinese Medicine and Hangzhou First People’s Hospital from 2005.01 to 2015.12. The clinic features were analyzed. Arterial blood gas analysis and disease severity score (DSS) before and after lung lavage were compared to evaluate the effect of lavage. PAP severity was based on arterial partial pressure of oxygen (PaO2), arterial oxygen saturation (SaO2), DSS, forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO). The correlation analysis was performed to estimate the relation of serum markers [carcinoembryonic antigen (CEA), cytokeratin fragment antigen 21-1 (CYFRA21-1), neuron specific enolase (NSE), lactate dehydrogenase (LDH), triglyceride (TG) et.al] and severity. Independent factors which could reflect PAP severity were explored by logistic regression analysis.Results:The common symptoms and signs were as follows:chest tightness and shortness of breath (65.3%), cough and phlegm (63.3%), impaired ventilatory function (44.8%), impaired diffusive function (66.7%), hypoxemia (66.7%). The levels of several serum markers were elevated:CEA (58.3%), CYFRA21-1 (57.7%), NSE (23.5%), LDH (39.1%) and TG (37.8%). Most patients revealed diffuse geographic ground-glass opacity on HRCT, and 35.3% patients presented characteristic "crazy paving" appearance. Fourteen patients received lung lavage and the symptoms and signs were improved. In nine patients arterial blood gas and DSS was evaluated before and after lavage. After lavage, the level of PaO2 increased and DSS decreased (p<0.05). The level of CEA had a significant correlation with DLCO (r=-0.701, p<0.001), PaO2 (r=-0.457, p=0.011) and DSS (r=0.420, p=0.021). The level of CYFRA21-1 had a significant correlation with PaO2 (r=-0.530, p=0.013), SaO2 (r=-0.488, p=0.034) and DSS (r=0.493, p=0.023). The level of NSE had a significant correlation with FVC (r=-0.689, p=0.019), DLCO (r=-0.698, p=0.025) and PaO2 (r=-0.579, p=0.049). The level of serum LDH had a significant correlation with FVC (r=-0.397, p=0.041), PaO2(r=-0.387, p=0.015), SaO2 (r=-0.392, p=0.014) and DSS (r=0.323, p=0.045). The level of TG had a significant correlation with FVC (r=-0.487, p=0.010) and DLCO (r=-0.518, p=0.008). Logistic regression analysis didn’t reveal any independent factors reflecting PAP severity. The levels of serum LDH and CEA in patients with DSS> 3 were higher than these in patients with DSS≤3 (p<0.05). The median of DLCO% predicted was 55.3%, and the levels of serum LDH, CEA, CYFRA21-1 and NSE were higher in patients with DLCO% <55.3% than these in patients with DLCO%≥55.3%(p<0.05).Conclusions:Clinical symptoms and signs of PAP were non-specific, but characteristic manifestations of chest HRCT, especially "crazy paving" appearance, contributed to the diagnosis. Lung lavage made significant improvement in clinical symptoms and signs. PaO2 was improved and DSS was decreased after lung lavage, which might be immediate and reliable indicators to evaluate effect in lavage. The levels of serum LDH, CYFRA21-1, NSE and CEA might be correlated with the severity of PAP.