The role of volatile organic compounds for assessing characteristics and severity of non-cystic fibrosis bronchiectasis: an observational study.

Background: Hypoxic conditions and Pseudomonas aeruginosa (P. aeruginosa) infection are significant factors influencing the prognosis and treatment of patients with bronchiectasis. This study aimed to explore the potential for breath analysis to detect hypoxic conditions and P. aeruginosa infection in bronchiectasis patients by analyzing of volatile organic compounds (VOCs) in exhaled breath condensate (EBC). Methods: EBC samples were collected from stable bronchiectasis patients and analyzed using solid phase microextraction-gas chromatography-mass spectrometry (SPME-GCMS). The association of VOCs with bronchiectasis patients' phenotypes including hypoxic conditions and P. aeruginosa isolation was analyzed, which may relate to the severity of bronchiectasis disease. Results: Levels of 10-heptadecenoic acid, heptadecanoic acid, longifolene, and decanol in the hypoxia group were higher compared to the normoxia group. Additionally, the levels of 13-octadecenoic acid, octadecenoic acid, phenol, pentadecanoic acid, and myristic acid were increased in P. aeruginosa (+) group compared to the P. aeruginosa (-) group. Subgroup analysis based on the bronchiectasis severity index (BSI)reveled that the levels of 10-heptadecenoic acid, heptadecanoic acid, decanol, 13-octadecenoic acid, myristic acid, and pentadecanoic acid were higher in the severe group compared to the moderate group. Multivariate linear regression showed that 10-heptadecenoic acid and age were independent prognostic factors for bronchiectasis patients with hypoxia. Furthermore, octadecenoic acid, phenol and gender were identified as independent prognostic factors for bronchiectasis patients with P. aeruginosa isolation. Conclusion: The study provides evidence that specific VOCs in EBC are correlated with the severity of bronchiectasis, and 10-heptadecenoic acid is shown to be a predictive marker for hypoxia condition in bronchiectasis patients.

Quality-of-Life Bronchiectasis Respiratory Symptom Scale Predicts the Risk of Exacerbations in Adults with Bronchiectasis: A Prospective Observational Study.

Rationale: The relationship between symptoms, measured using a validated disease-specific questionnaire, and longitudinal exacerbation risk has not been demonstrated in bronchiectasis. Objectives: The aim of this study is to investigate whether baseline symptoms, assessed using the Quality-of-Life Bronchiectasis Respiratory Symptom Scale (QoL-B-RSS) and its individual component scores, could predict future exacerbation risk in patients with bronchiectasis. Methods: The study included 436 adults with bronchiectasis from three tertiary hospitals. Symptoms were measured using the QoL-B-RSS, with scores ranging from 0 to 100, where lower scores indicated more severe symptoms. We examined whether symptoms as continuous measures were associated with the risk of exacerbation over 12 months. The analysis was also repeated for individual components of the QoL-B-RSS score. Results: The baseline QoL-B-RSS score was associated with an increased risk of exacerbations (rate ratio, 1.25 for each 10-point decrease; 95% confidence interval [CI], 1.15-1.35; P < 0.001), hospitalizations (rate ratio, 1.24; 95% CI, 1.05-1.43; P = 0.02), and reduced time to the first exacerbation (hazard ratio, 1.12; 95% CI, 1.03-1.21; P = 0.01) over 12 months, even after adjusting for relevant confounders, including exacerbation history. The QoL-B-RSS score was comparable to exacerbation history in its association with future frequent exacerbations (defined as three or more exacerbations per year) and hospitalization (area under the curve, 0.86 vs. 0.84; P = 0.46; and area under the curve, 0.81 vs. 0.83; P = 0.41, respectively). Moreover, patients with more severe symptoms in the majority of individual components of the QoL-B-RSS were more likely to experience exacerbations. Conclusions: Symptoms can serve as useful indicators for identifying patients at increased risk of exacerbation in bronchiectasis. Beyond relying solely on exacerbation history, a comprehensive assessment of symptoms could facilitate timely and cost-effective implementation of interventions for exacerbation prevention.

Vitamin B6 regulates IL-33 homeostasis to alleviate type 2 inflammation.

Interleukin-33 (IL-33) is a crucial nuclear cytokine that induces the type 2 immune response and maintains immune homeostasis. The fine-tuned regulation of IL-33 in tissue cells is critical to control of the type 2 immune response in airway inflammation, but the mechanism is still unclear. Here, we found that healthy individuals had higher phosphate-pyridoxal (PLP, an active form of vitamin B6) concentrations in the serum than asthma patients. Lower serum PLP concentrations in asthma patients were strongly associated with worse lung function and inflammation. In a mouse model of lung inflammation, we revealed that PLP alleviated the type 2 immune response and that this inhibitory effect relied on the activity of IL-33. A mechanistic study showed that in vivo, pyridoxal (PL) needed to be converted into PLP, which inhibited the type 2 response by regulating IL-33 stability. In mice heterozygous for pyridoxal kinase (PDXK), the conversion of PL to PLP was limited, and IL-33 levels were increased in the lungs, aggravating type 2 inflammation. Furthermore, we found that the mouse double minute 2 homolog (MDM2) protein, an E3 ubiquitin-protein ligase, could ubiquitinate the N-terminus of IL-33 and sustain IL-33 stability in epithelial cells. PLP reduced MDM2-mediated IL-33 polyubiquitination and decreased the level of IL-33 through the proteasome pathway. In addition, inhalation of PLP alleviated asthma-related effects in mouse models. In summary, our data indicate that vitamin B6 regulates MDM2-mediated IL-33 stability to constrain the type 2 response, which might help develop a potential preventive and therapeutic agent for allergy-related diseases.

Updated severity and prognosis score of pulmonary alveolar proteinosis: A multi-center cohort study in China.

Background: The high-resolution computed tomography (HRCT) score is an important component of the severity and prognosis score of pulmonary alveolar proteinosis (SPSP). However, the HRCT score in SPSP only considers the extent of opacity, which is insufficient. Methods: We retrospectively evaluated HRCT scores for 231 patients with autoimmune pulmonary alveolar proteinosis (APAP) from three centers of the China Alliance for Rare Diseases. The SPSPII was created based on the overall density and extent, incorporating the SPSP. The severity of APAP patients was assessed using disease severity scores (DSS), SPSP, and SPSPII to determine the strengths and weaknesses of the different assessment methods. We then prospectively applied the SPSPII to patients before treatment, and the curative effect was assessed after 3 months. Results: The HRCT overall density and extent scores in our retrospective analysis were higher than the extent scores in all patients and every original extent score severity group, as well as higher related to arterial partial oxygen pressure (PaO2) than extent scores. The mild patients accounted for 61.9% based on DSS 1-2, 20.3% based on SPSP 1-3, and 20.8% based on SPSPII 1-3. Based on SPSP or SPSPII, the number of severe patients deteriorating was higher in the mild and moderate groups. When applied prospectively, arterial PaO2 differed between any two SPSPII severity groups. The alveolar-arterial gradient in PaO2 (P[A-a]O2), % predicted carbon monoxide diffusing capacity of the lung (DLCO), and HRCT score were higher in the severe group than in the mild and moderate groups. After diagnosis, mild patients received symptomatic treatment, moderate patients received pure whole lung lavage (WLL) or granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy, and severe patients received WLL and GM-CSF therapy. Importantly, the SPSPII in mild and severe groups were lower than baseline after 3 months. Conclusion: The HRCT density and extent scores of patients with APAP were better than the extent score. The SPSPII score system based on smoking status, symptoms, PaO2, predicted DLCO, and overall HRCT score was better than DSS and SPSP for assessing the severity and efficacy and predicting the prognosis. Trial registration: ClinicalTrial.gov, identifier: NCT04516577.

Altered fecal microbiome and metabolome in adult patients with non-cystic fibrosis bronchiectasis.

BACKGROUND: Emerging experimental and epidemiological evidence highlights a crucial cross-talk between the intestinal flora and the lungs, termed the "gut-lung axis". However, the function of the gut microbiota in bronchiectasis remains undefined. In this study, we aimed to perform a multi-omics-based approach to identify the gut microbiome and metabolic profiles in patients with bronchiectasis. METHODS: Fecal samples collected from non-CF bronchiectasis patients (BE group, n = 61) and healthy volunteers (HC group, n = 37) were analyzed by 16 S ribosomal RNA (rRNA) sequencing. The BE group was divided into two groups based on their clinical status: acute exacerbation (AE group, n = 31) and stable phase (SP group, n = 30). Further, metabolome (lipid chromatography-mass spectrometry, LC-MS) analyses were conducted in randomly selected patients (n = 29) and healthy volunteers (n = 31). RESULTS: Decreased fecal microbial diversity and differential microbial and metabolic compositions were observed in bronchiectasis patients. Correlation analyses indicated associations between the differential genera and clinical parameters such as bronchiectasis severity index (BSI). Disease-associated gut microbiota was screened out, with eight genera exhibited high accuracy in distinguishing SP patients from HCs in the discovery cohort and validation cohort using a random forest model. Further correlation networks were applied to illustrate the relations connecting disease-associated genera and metabolites. CONCLUSION: The study uncovered the relationships among the decreased fecal microbial diversity, differential microbial and metabolic compositions in bronchiectasis patients by performing a multi-omics-based approach. It is the first study to characterize the gut microbiome and metabolome in bronchiectasis, and to uncover the gut microbiota's potentiality as biomarkers for bronchiectasis. TRIAL REGISTRATION:  This study is registered with ClinicalTrials.gov, number NCT04490447.

CYFRA21-1 is a more sensitive biomarker to assess the severity of pulmonary alveolar proteinosis.

BACKGROUND: Serum lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA) and CYFRA21-1 are the commonly used biomarkers to identify patients with autoimmune pulmonary alveolar proteinosis (APAP). However, it is not clear which of the biomarkers is more sensitive to the severity of the patient's condition. METHODS: APAP patients numbering 151 were enrolled in this study. All patients' severity was assessed through the severity and prognosis score of PAP (SPSP). According to the respective laboratory upper limits of serum levels of LDH, CEA and CYFRA21-1, APAP patients were divided into higher and lower-level groups. Patients were divided into five groups based on SPSP. 88 patients had completed six months of follow-up. We calculated sensitivity, specificity, and critical point of LDH, CEA and CYFRA21-1 between APAP patients and normal control group, and between grade 1-2 and 3-5 through receiving operating characteristics (ROC) curve. RESULTS: Serum LDH, CEA and CYFRA21-1 levels of patients with PAP were higher and distinctly related to PaO2, FVC, FEV1, DLCO, HRCT scores and SPSP. The SPSP of patients in higher-level LDH, CEA and CYFRA21-1 groups were higher than those of corresponding lower-level groups. Based on SPSP results, the patients were divided into five groups (grade I, 20; grade II, 37; grade III, 40; grade IV, 38; grade V, 16). The serum level of CYFRA21-1 of patients with APAP in grade II was higher than that of patients in grade I and lower than that of patients in grade III. Serum CYFRA21-1 of patients with APAP after six months were higher than the baseline among the aggravated group. Serum LDH, CEA and CYFRA21-1 levels after six months among patients in the relieved group of patients with APAP were lower than the baseline. ROC correlating LDH, CEA and CYFRA21-1 values with APAP severity (between grade 1-2 and 3-5) showed an optimal cutoff of LDH of over 203 U/L (< 246 U/L), CEA of over 2.56 ug/L (< 10 ug/L), and CYFRA21-1 of over 5.57 ng/ml (> 3.3 ng/ml) (AUC: 0.815, 95% CI [0.748-0.882], sensitivity: 0.606, specificity: 0.877). CONCLUSION: Serum CYFRA21-1 level was more sensitive in revealing the severity of APAP than LDH and CEA levels among mild to moderate forms of disease.

Bronchoscopic airway clearance therapy for acute exacerbations of bronchiectasis.

BACKGROUND: Persistent cough and large amounts of purulent sputum affects many bronchiectasis patients. No studies have evaluated the efficacy and safety of bronchoscopic airway clearance therapy and bronchoalveolar lavage (B-ACT) for non-cystic fibrosis bronchiectasis patients with acute exacerbation. METHODS: A randomised controlled trial was conducted to explore the efficacy and safety of B-ACT among 189 bronchiectasis inpatients from February 1, 2018 to February 28, 2019. The primary outcome was the time to first acute exacerbation. Secondary outcomes included changes of health-related scores, length of hospital stay, hospitalization expenses and incidences of adverse events. FINDINGS: B-ACT therapy significantly prolonged the median days to first acute exacerbation when compared with control group (198 vs 168 days, HR 0·555 (0·322-0·958), p=0·012; effect size(r)= 0·94). Further analysis showed that B-ACT therapy was more beneficial for these patients with severe disease and greater symptoms. COPD Assessment Test (CAT) scores improved significantly on the third day (5·45 vs 4·85, 0·60 (0·09-1·11), p=0·023), and Leicester Cough Questionnaire (LCQ) scores improved obviously on the third and seventh days (1·53 vs 1·23, 0·30 (0·05-0·55), p=0·044; 1·66 vs 1·32, 0·34 (0·08-0·60), p=0·022; respectively) after B-ACT therapy. Adverse events associated with B-ACT were mostly transient and mild. Differences of the lengths of hospital stay and hospitalization expenses in both group was not significant. INTERPRETATION: B-ACT therapy significantly prolonged the time to first acute exacerbation after discharge, highlighting the importance of B-ACT therapy focused on symptom improvements in preventing exacerbation. FUNDING: National Natural Science Foundation of China. TRIAL REGISTRY: ClinicalTrials.gov; No.:NCT03643302; URL: www.clinicaltrials.gov.

The clinical characteristics and prognosis of ABPA are closely related to the mucus plugs in central bronchiectasis.

INTRODUCTION: The characteristics of Allergic Bronchopulmonary Aspergillosis (ABPA) based on its radiological classification is still unclear. OBJECTIVES: To investigate the clinical significances of ABPA patients with central bronchiectasis (ABPA-CB) by different radiological classifications of mucus plugs. METHODS: ABPA-CB patients from a pulmonary hospital between 2008 and 2015 were retrospectively included and analysed. According to the chest imaging in their first visit to physician, the ABPA-CB patients were divided into two groups based on the presence of high-attenuation mucus (HAM) or low-attenuation mucus (LAM). The primary endpoint was ABPA relapse within 1 year since the glucocorticoid withdrawal. The relationship between the imaging findings and the clinical prognosis was illuminated. RESULTS: A total of 125 ABPA patients were analysed in this study. Compared to the LAM group, the HAM group presented higher blood eosinophil cells counts, higher rates of Aspergillus detection isolated in sputum and expectoration of brownish-black mucus plugs, more affected lobes and segments, poorer pulmonary function and higher rate of relapse. CONCLUSIONS: The clinical characteristics and prognosis of ABPA-CB patients are closely related to its radiological phenotype of mucus plugs in the central bronchiectasis. Clinicians should promote a diversity of personalized treatments for different patients with different radiological characteristics.

Viral infection in community acquired pneumonia patients with fever: a prospective observational study.

BACKGROUND: Patients with community acquired pneumonia (CAP) caused by viruses can develop severe complications, which result in hospitalization and death. The purpose of this study was to analyse the aetiology, incidence, clinical characteristics, and outcomes of CAP patients with fever during non-pandemics, and then to provide theoretical basis for accurate diagnosis and treatment in CAP patients. METHODS: An enrolment system was established for monitoring the CAP patients with fever. Multiplex polymerase chain reaction (mPCR) kits were used to detect 10 viruses [influenza A and B, adenovirus (ADV), respiratory syncytial virus (RSV) A and B, picornavirus, parainfluenza virus (PIV), coronavirus, human metapneumovirus (HMPV), and bocavirus]. Data on age, gender, underlying diseases, complications, laboratory indexes, and outcomes were collected by physicians. RESULTS: This prospective study included 320 patients with fever. Among them, 23.4% were viral-positive by mPCR, with influenza virus most prominent followed by picornavirus. Strong variation in seasonal distribution was shown in viral infections, with peak months from December to February. Patients with influenza infection were likely to be taken to emergency rooms and have respiratory failure with higher creatinine kinase levels and lower white blood cell counts. Streptococcus pneumoniae followed by haemophilus influenzae were the most common bacteria in viral co-infections, which accounted for one third of virus-positive patients. Viral CAP and mixed CAP were not independent factors for death. In addition, lactate dehydrogenase (LDH) >246 IU/L [odds ratio (OR) =7.06, 95% confidence interval (CI): 2.15-23.2, P=0.001], and serum calcium <2.18 mmol/L (OR =6.67, 95% CI: 1.42-31.3, P=0.016) were associated with death. CONCLUSIONS: Viruses play an important role in CAP patients with fever, a systematic clinical, radiological and biological analysis of these patients can contribute to effective therapy that may prevent the development of CAP and improve the outcomes. The present work showed an elaborate analysis evidence of viral infection among fever CAP inpatients.

Clinical characteristics and validation of bronchiectasis severity score systems for post-tuberculosis bronchiectasis.

INTRODUCTION: Lung damage related to tuberculosis is a major contributor to the etiology of bronchiectasis in China. It is unknown whether bronchiectasis severity score systems are applicable in these cases. OBJECTIVES: To evaluate the clinical characteristics and validation of bronchiectasis severity score systems for post-tuberculosis bronchiectasis. METHODS: The study enrolled 596 bronchiectasis patients in Shanghai Pulmonary Hospital between January 2011 and December 2012. The data for calculating FACED and bronchiectasis severity index (BSI) scores along with mortality, readmission, and exacerbation outcomes were collected and analyzed within a follow-up period with a median length of 48 months (interquartile range 43-54 months). RESULTS: The study enrolled 101 post-tuberculosis bronchiectasis patients and 495 non-tuberculosis bronchiectasis patients. Compared with non-post-tuberculosis bronchiectasis, post-tuberculosis bronchiectasis patients experienced less bilateral bronchiectasis (P = .004), a higher frequency of right upper lobe involvement (P < .001) and showed the cylindrical type more often (P < .001). Follow-up data indicated that both scoring systems were able to predict 48(43-54) month mortality in post-tuberculosis patients as assessed by the area under the receiver operator characteristic curve (AUC) (FACED AUC = 0.81, BSI AUC = 0.70), but they did not predict readmission (FACED and BSI = 0.56) or exacerbation (FACED and BSI = 0.52) well. CONCLUSIONS: There are apparent differences on radiologic features between bronchiectasis patients with and without history of pulmonary tuberculosis. Both FACED and BSI can predict mortality in post-tuberculosis bronchiectasis.

Smoking cessation affects the natural history of COPD.

BACKGROUND: Cigarette smoking is the most commonly encountered and readily identifiable risk factor for COPD. However, it is not clear which quantitative factors related to smoking influence the prognosis of COPD patients. METHODS: A total of 204 patients with a long-term history of smoking were enrolled into this study and followed up for 5 years. Patients were divided into "death" or "survival" groups based on follow-up results and "quitting-smoking" or "continuing-smoking" groups based on whether they gave up smoking. RESULTS: Patients in the death group had a longer smoking time, lower prevalence of quitting smoking, later onset of COPD symptoms, older age at quitting smoking, lower forced expiratory volume in one second (FEV1) % predicted, and lower ratio of FEV1/forced vital capacity. Age, age at quitting smoking, and FEV1% predicted were independently associated with mortality from COPD. Compared to the continuing-smoking group, the quitting-smoking group had a lower mortality rate, longer course of COPD, earlier onset of COPD symptoms, and lower residual volume percent predicted. During the 5-year follow-up, 113 deaths were recorded (quitting-smoking group: n=92; 40 deaths; continuing-smoking group: n=112; 73 deaths). The mortality risk remained significantly higher in the continuing-smoking group than the quitting-smoking group (log-rank test, 13.59; P=0.0002). CONCLUSION: Smoking time may be related to the mortality rate from COPD. Smoking cessation has the greatest capacity to influence the natural history of COPD.

Immunity status of invasive pulmonary aspergillosis patients with structural lung diseases in Chinese adults.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a fungal infection frequently observed in patients with immune dysfunction, such as those suffering from structural lung diseases. Nevertheless, studies assessing IPA combined with other common respiratory diseases remain scarce, particularly those regarding the immune status of its patients. Different structural lung diseases are known to differently affect patient immune status; however, the mechanisms by which this is conferred have yet to be determined. Thus, our study aims to compare the immune status of IPA patients with the structural lung diseases chronic obstructive pulmonary diseases (COPD), interstitial lung disease (ILD) and non-cystic fibrosis bronchiectasis (NCFB). METHODS: This study was performed retrospectively with data collected over the years 2004 to 2013 at Shanghai Pulmonary Hospital, Tongji University, and included 77 patients whose lower respiratory tract (LRT) samples tested positive for. Our analysis considered blood examinations of CD3+, CD4+, CD8+, CD4+/CD8+, IgG, IgA and IgM levels. RESULTS: CD4+/CD8+ double positive cells, representing cell-mediated immunity, were less abundant in IPA patients with COPD than those with ILD and NCFB (0.81±0.09 vs. 1.39±0.25 and 0.81±0.09 vs. 1.57±0.06, respectively, P<0.001). In agreement with this result, corticosteroid and broad-spectrum antibiotic use were most common in individuals with COPD (57%). IgA levels, which indicate humoral immunity, were lower in IPA patients with NCFB than those with COPD or ILD (0.95±0.28 vs. 1.64±0.40 g/L and 0.95±0.28 vs. 3.16±0.83 g/L, respectively, P<0.001). CONCLUSIONS: Immunity status differs between IPA patients with different structural lung diseases. Among IPA patients with COPD, ILD and NCFB, those with COPD have the lowest cell-mediated immunity, while those with NCFB have the lowest humoral immunity.

Pathogen characteristics reveal novel antibacterial approaches for interstitial lung disease.

Interstitial lung disease (ILD) is a clinical disorder associated with changes of lung structure. Concurrent infection is a serious complication and one of the major factors that exacerbates ILD. Pathogen screening is a critical step in early diagnosis and proper treatment of ILD with secondary infection. Here we analyzed distribution and drug susceptibility of pathogens isolated from hospitalized ILD patients from January, 2007 to December, 2008 and compared them to bacterial drug resistance data in CHINET during the same period. The main specimens were from sputum culture, lavage fluid culture, lung biopsy tissue culture, and pleural effusion culture and bacterial or fungal cultures were performed on these specimens accordingly. Drug susceptibility was tested for positive bacterial cultures using disk diffusion (Kirby-Bauer method) and E Test strips in which results were determined based on the criteria of CLSI (2007). A total of 371 pathogen strains from ILD patients, including 306 bacterial strains and 65 fungal strains were isolated and cultured. Five main bacterial strains and their distribution were as follows: Klebsiella pneumoniae (31.7%), Pseudomonas aeruginosa (20.6%), Acinetobacter (12.7%), Enterobacter cloacae (8.2%), and Staphylococcus aureus (7.8%). The results showed that ILD patients who had anti-infection treatment tended to have Gram-negative bacteria, whether they acquired an infection in the hospital or elsewhere. Drug resistance screening indicated that aminoglycosides and carbapenems had lower antibiotic resistance rates. In addition, we found that the usage of immunosuppressants was associated with the increased infection rate and number of pathogens that were isolated. In conclusion, aminoglycosides and carbapenems may be selected as a priority for secondary infection to control ILD progression. Meanwhile, the use of anti-MRSA/MRCNS drugs may be considered for Staphylococcus infection.

[The pulmonary expression of granulocyte-macrophage colony-stimulating factor and surfactant protein in adult idiopathic pulmonary alveolar proteinosis].

OBJECTIVE: To investigate the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), GM-CSF/IL-3/IL-5 receptor common beta chain (GM-CSFbetacR), surfactant protein (SP)-A and SP-D in adult patients with idiopathic pulmonary alveolar proteinosis (PAP), so as to demonstrate the possible association of GM-CSF, GM-CSFbetacR, SP-A and SP-D with human PAP. METHODS: The protein expression of GM-CSF, GM-CSFbetacR, SP-A and SP-D in the alveolar macrophages and alveolar type II epithelial cells was detected by immunohistochemical staining. RESULTS: The age was 51.8 +/- 9.5 years old for patients with idiopathic PAP (6; males 4, females 2) and 48.8 +/- 12.6 years old for the control adult individuals (6; males 4, females 2). There was no difference in the expression of GM-CSF (P = 0.818) and SP-D (P = 0.24) in alveolar macrophages between patients with idiopathic PAP and the controls. The expression of GM-CSFbetacR (P = 0.002) and SP-A (P = 0.004) in alveolar macrophages of patients with idiopathic PAP was less than that in the controls. There was no expression of GM-CSF in alveolar type II epithelial cells of patients with idiopathic PAP and the controls. There was a little expression of GM-CSFbetacR in alveolar type II epithelial cells of the controls. There was no expression of GM-CSFbetacR in alveolar type II epithelial cells of patients with idiopathic PAP. There was no difference in the expression of SP-A (P = 0.818) and SP-D (P = 0.485) in alveolar type II epithelial cells between patients with idiopathic PAP and the controls. CONCLUSION: The decreased protein expression of GM-CSFbetacR in alveolar macrophages may be one of the mechanisms causing dysfunction of the macrophages in adult patients with idiopathic PAP.