Integrated approach to bronchoalveolar lavage cytology to distinguish interstitial lung diseases

BackgroundBroncho-alveolar lavage (BAL) is a safe diagnostic procedure, useful for differentiating fibrotic lung disorders and for excluding malignancy and infection. A recent multicenter study demonstrated a new, relatively sensitive, and specific index called Bronchoalveolar Cytology Threshold (BCT), useful for distinguishing healthy individuals from patients with lung diseases.ObjectivesIn our study, BCT was applied for the first time to the analysis of interstitial lung diseases (ILDs), investigating its potential for differential diagnosis. Combinations of BAL cells that improve diagnostic accuracy for ILDs were studied and are proposed.MethodsA retrospective analysis of BAL samples was performed. We considered more than 1000 BAL samples from patients investigated for ILD, performed at Siena University Hospital.The samples enrolled for the study included 468 patients: 413 with and 55 without ILD. BAL was performed for diagnostic purposes in line with international guidelines. BCT were calculated according to available literature.ResultsAmong ILDs, patients with fibrotic hypersensitivity pneumonitis, idiopathic pulmonary fibrosis (IPF) and sarcoidosis showed significantly lower BCTs than unclassified ILD. Asbestosis patients showed significantly lower BCTs than nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP), connective tissue disease related ILD (CTD-ILD), sarcoidosis and unclassified ILD patients. COP patients showed significantly higher BCT than IPF, f-HP and sarcoidosis. Moreover, COP patients were best distinguished by BCT.ConclusionThe analysis of BAL features is currently included in the diagnostic algorithm of ILDs. BAL cell patterns and BCT index can provide useful information for distinguishing ILDs, reducing the need for invasive procedures. Integrated approaches to BAL analysis can improve the interpretation of results without further cost or loss of time.     

Acute and subacute idiopathic interstitial pneumonias

Idiopathic interstitial pneumonias (IIPs) may have an acute or subacute presentation, or acute exacerbation may occur in a previously subclinical or unrecognized chronic IIP. Acute or subacute IIPs include acute interstitial pneumonia (AIP), cryptogenic organizing pneumonia (COP), nonspecific interstitial pneumonia (NSIP), acute exacerbation of idiopathic pulmonary fibrosis (AE‐IPF) and AE‐NSIP. Interstitial lung diseases (ILDs) including connective tissue disease (CTD) associated ILD, hypersensitivity pneumonitis, acute eosinophilic pneumonia, drug‐induced lung disease and diffuse alveolar haemorrhage need to be differentiated from acute and subacute IIPs. Despite the severe lack of randomized controlled trials for the treatment of acute and subacute IIPs, the mainstream treatment remains corticosteroid therapy. Other potential therapies reported in the literature include corticosteroids and immunosuppression, antibiotics, anticoagulants, neutrophil elastase inhibitor, autoantibody‐targeted treatment, antifibrotics and hemoperfusion therapy. With regard to mechanical ventilation, patients in recent studies with acute and subacute IIPs have shown better survival than those in previous studies. Therefore, a careful value‐laden decision about the indications for endotracheal intubation should be made for each patient. Noninvasive ventilation may be beneficial to reduce ventilator associated pneumonia.     

Anti-endothelial cell antibodies in patients with interstitial lung diseases

BACKGROUND: Anti-endothelial cell antibodies (AECA) are circulating antibodies that bind to endothelial antigens and induce endothelial cell damage. AECA have been detected in patients with collagen vascular disease (CVD) and their presence is associated with interstitial lung disease (ILD) in cases of CVD. However, the prevalence of AECA in patients with idiopathic interstitial pneumonias (IIPs) is not known. METHODS: We investigated the prevalence of AECA in patients with IIPs. We also examined whether the expression of AECA differed among the histologic subgroups usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP), and compared the values with those of CVD-associated ILD (CVD-ILD). Twenty patients with IIPs and 24 patients with CVD-ILD were studied. Serum samples were examined for AECA by cellular enzyme-linked immunosorbent assay (ELISA) using human umbilical vein endothelial cells. Values are expressed as ELISA ratios (ER). RESULTS: All sera from patients with idiopathic pulmonary fibrosis (IPF)/UIP were negative for AECA, whereas 5 out of 10 with idiopathic NSIP, 5 out of 14 with CVD-UIP and 4 out of 10 with CVD-NSIP tested positive (p<0.05). ER values were significantly lower in patients with IPF/UIP than idiopathic NSIP, CVD-UIP or CVD-NSIP (p<0.05). Among idiopathic NSIP, CVD-NSIP and CVD-UIP patients, the ER values did not differ. CONCLUSIONS: Among IIP patients, only those with idiopathic NSIP, not IPF/UIP, tested positive for AECA. The prevalence of AECA in idiopathic NSIP patients was similar to that in CVD-ILD patients. These results may provide important information to understand the distinct pathophysiology of each form of IIPs.     

Is Metalloproteinase-7 Specific for Idiopathic Pulmonary Fibrosis?

BACKGROUND: Matrix metalloproteinase (MMP)-7 was reported to be a key molecule in the pathogenesis of idiopathic pulmonary fibrosis (IPF) based on the result of microarray analysis and knockout mice. However, the role of MMP-7 has not been determined in other types of idiopathic interstitial pneumonia (IIP). The aim of this study was to investigate the role of MMP-7 in IIP by comparing its expression in usual interstitial pneumonia (UIP) and cryptogenic organizing pneumonia (COP). METHODS: Levels of MMP and tissue inhibitors of metalloproteinase in BAL fluid and their expression on lung tissues were compared between normal control subjects (n = 5) and the patients with IPF (n = 6) and COP (n = 11). RESULTS: There was no significant difference in BAL fluid MMP-7 levels between UIP and COP, although it was higher in both diseases compared to normal control subjects. Furthermore, the pattern and the degree of MMP-7 expression in lung tissues were also similar in both IPF and COP, whereas MMP-2 level was higher in COP and MMP-9 level was higher in IPF. CONCLUSION: MMP-7 seems to play an important role in the pathogenesis of not only IPF but also COP; therefore, it may not be the key factor determining the prognosis or reversibility of IIPs.     

Prognosis of fibrotic interstitial pneumonia: idiopathic versus collagen vascular disease-related subtypes

BACKGROUND: To investigate whether the better prognosis of interstitial pneumonias associated with collagen vascular disease (CVD) compared with idiopathic interstitial pneumonia (IIP) is due to higher frequency of the nonspecific interstitial pneumonia (NSIP) pattern in CVD, we compared the outcomes of patients from these two groups with the same histopathologic pattern. SUBJECTS: The clinical features and survival of 362 patients (269 with IIP and 93 with CVD) diagnosed using surgical lung biopsy were analyzed. RESULTS: The mean survival of the CVD group (131.0 mo) was longer than that of the IIP group (80.5 mo) (p<0.0001). The patients with usual interstitial pneumonia pattern among the CVD group (n=36) was younger, female, and predominantly nonsmoking compared with the IIP group (n=203). Although baseline lung functions were not significantly different, the CVD group survived longer (mean, 177.0 mo) than the IIP group (mean, 66.9 +/- 6.5 mo; p=0.001). By multivariate analysis, younger age, better pulmonary function, and the presence of a CVD were independent prognostic factors. In NSIP pattern, no significant differences in survival, clinical features, or lung function were found between the two groups. CONCLUSION: Our data suggest that the better prognosis of patients in the CVD group is not solely due to the predominance of the NSIP pattern. The prognosis of patients with the usual interstitial pneumonia pattern in CVD is better than in those with idiopathic pulmonary fibrosis, despite the same pathologic pattern. In contrast, in those with an NSIP pattern, the prognosis is similar in both groups.     

Evaluation of CD30 as a marker for th2 lymphocytes in bronchoalveolar lavage in interstitial lung diseases

Several studies have been carried out to clarify the relationship between CD30 expression and Th2 lymphocytes, although the results have been controversial. To investigate whether CD30 is a useful marker for Th2 lymphocytes in bronchoalveolar lavage (BAL) in interstitial lung diseases (ILD), we studied six control subjects and 31 patients with ILD (12 with idiopathic pulmonary fibrosis, seven with hypersensitivity pneumonitis, three with chronic eosinophilic pneumonia and nine with sarcoidosis). The levels of interleukin-5 (IL-5) (secreted by Th2 cells), interferon-gamma (IFNgamma) (secreted by Th1 cells) and the expression of CD30 on lymphocytes were determined in BAL fluid. There were no differences in the percentage of CD30+ lymphocytes between controls and patients with ILD (0.8+0.4% vs. 2+/-0.4%). In order to determine the relationship between Th2 cells and CD30 expression, we divided the patients into two groups according to BAL IL-5 levels. Group I consisted of eight patients (three chronic eosinophilic pneumonia, three hypersensitivity pneumonitis, two idiopathic pulmonary fibrosis) with high IL-5 levels (298+/-138 pg ml(-1)). Group II consisted of the remaining 23 ILD patients with normal IL-5 levels (0.9+/-0.6 pg ml(-1)). The percentage of eosinophils in BAL fluid was significantly higher in group I compared with group 11 (34+/-16% vs. 3+/-1%, P < 0.05). A correlation between CD30+ lymphocytes and IL-5 in group 1 was not shown. There were no differences in the number of CD30+ I we found a significant correlation between IL-5 levels and the percentage of eosinophils (r = 0.95, P < 0.0001). Our results suggest that CD30 does not appear to be a useful marker for Th2 lymphocytes in BAL from patients with ILD.     

Utility of KL-6/MUC1 in the clinical management of interstitial lung diseases

Interstitial lung diseases (ILDs) are a diverse group of pulmonary disorders characterized by various patterns of inflammation and fibrosis in the interstitium of the lung. Because injury and/or regeneration of type II pneumocytes are prominent histological features of ILDs, substances derived from type II pneumocytes have been the focus of research investigating potential biomarkers for ILD. One important biomarker for ILD is the high-molecular-weight glycoprotein, Krebs von den Lungen-6 (KL-6). KL-6 is now classified as a human MUC1 mucin protein, and regenerating type II pneumocytes are the primary cellular source of KL-6/MUC1 in the affected lungs of patients with ILD. KL-6/MUC1 is detectable in the serum of patients with ILD, and extensive investigations performed primarily in Japan have revealed that serum KL-6/MUC1 is elevated in 70-100% of patients with various ILDs, including idiopathic interstitial pneumonias, collagen vascular disease-associated interstitial pneumonia, hypersensitivity pneumonia, radiation pneumonitis, drug-induced ILDs, acute respiratory distress syndrome, pulmonary sarcoidosis, and pulmonary alveolar proteinosis. The results from these various studies have supported the utility of KL-6/MUC1 as a serum biomarker for detecting these various ILDs. Moreover, KL-6/MUC1 serum levels have been demonstrated to be useful for evaluating disease activity and predicting the clinical outcomes of various ILD types. Based on these observations, we believe that KL-6/MUC1 is currently one of the best and most reliable serum biomarkers available for ILD management.     

Detección de autoanticuerpos en el lavado broncoalveolar en pacientes con enfermedad pulmonar intersticial difusa

IntroductionSerum autoantibodies support the diagnosis of interstitial lung disease (ILD) related to systemic autoimmune diseases (SAD-ILD). Nevertheless, their presence in the bronchoalveolar lavage (BAL) has not been explored.ObjectivesTo demonstrate the presence of autoantibodies in the BAL of ILD patients at onset of clinical evaluation, its relation with serum autoantibodies and to analyze clinical features of patients with autoantibodies in BAL.MethodsAutoantibodies against extractable nuclear antigens (ENAs) were analyzed by immunoblot in the BAL of 155 patient with suspected diagnosis of ILD and 10 controls.ResultsSeven ENAs were detected in the BAL of 19 patients (Anti-Ro52, Anti-Ro60, CENP-B, Anti-La, Jo-1, Sm/RNP and Anti-SL70). The most frequent ENA was anti-Ro52 (13 patients; 68,4% of positives ones). Seven patients presented more than one ENAs. Fourteen were diagnosed of SAD-ILD, 3 of interstitial pneumonia with autoimmune features, one of non-specific idiopathic pneumonia and other of silicosis. In 10 cases (52%) IgA autoantibodies were also detected. The autoantibodies observed in BAL were also detected in the serum of 17 patients (90%). There were no significant clinical differences with the patients with SAD-ILD or interstitial pneumonia with autoimmune features with patients with negative BAL.ConclusionThe study of ENAs in BAL is feasible and can be a useful tool in the ILD initial algorithm, specifically sustaining the suspected diagnosis of SAD-ILD.     

Clinical significance of MCP-1 levels in BALF and serum in patients with interstitial lung diseases.

It has previously been reported that the expression of monocyte chemoattractant protein-1 (MCP-1) in the lung tissues of patients with idiopathic pulmonary fibrosis (IPF) was different from that in the tissues of patients with other interstitial lung diseases (ILDs). The aim of this study was to determine whether this difference reflects the amount of MCP-1 in the bronchoalveolar lavage fluid (BALF) or serum of patients with ILD, and whether such a correlation, if it exists, is clinically useful. MCP-1 concentrations in the BALF and sera were evaluated in 86 patients with ILDs including IPF, acute interstitial pneumonia, interstitial pneumonia with collagen vascular disease (IP-CVD), chronic interstitial pneumonia (CIP), bronchiolitis obliterans-organizing pneumonia, sarcoidosis, hypersensitivity pneumonitis, and in 10 normal healthy volunteers who were controls (NC). BALF MCP-1 levels were significantly elevated in the IPF, IP-CVD, CIP and sarcoidosis groups compared with the NC group. The level in the IPF group was significantly higher than that in any other patient group. Serum MCP-1 levels in the IPF, IP-CVD, CIP and sarcoidosis groups were significantly higher than the NC group. No statistical difference was found in serum MCP-1 levels between the IPF, IP-CVD and CIP groups. BALF MCP-1 levels were significantly higher than serum MCP-1 levels in the IPF group and lower than in the IP-CVD and CIP groups. Serum MCP-1 levels correlated with the clinical course of ILD treated with corticosteroid therapy. These results show that measurement of monocyte chemoattractant protein-1 levels in both bronchoalveolar lavage fluid and serum may be helpful in discriminating idiopathic pulmonary fibrosis from other types of interstitial lung disease and that monitoring of serum monocyte chemoattractant protein-1 may be useful for predicting the clinical course of interstitial lung diseases.     

Interstitial lung diseases: characteristics at diagnosis and mortality risk assessment

As the diagnostic assessment of the different forms of interstitial lung disease (ILD) is similar, this study aims to compare age, sex, the functional and broncho-alveolar lavage fluid (BALF) findings at diagnosis between the different forms of ILDs. In addition we want to determine which of these variables determine survival. We evaluated 315 patients (176 males and 139 females) in whom the diagnosis was made of sarcoidosis (n = 87), ILD due to connective tissue disease (n = 56), hypersensitivity pneumonitis (n = 50), idiopathic pulmonary fibrosis (IPF) (n = 64), other forms of idiopathic interstitial pneumonia (n = 29) or ILD due to an undefined form of fibrosis (n = 29). We analysed the role on outcome of type of disease, gender, age at diagnosis, type of cells in BALF, FVC and DLCO. In a Kaplan-Meier analysis IPF has the worst outcome in comparison with other types of ILDs. A Cox regression analysis showed that type of ILD, FVC, age at diagnosis and % of macrophages in BALF predict outcome of patients affected by ILD.     

The significance of the heparin precipitable fraction in lung diseases]

The authors recently experienced a case of idiopathic interstitial pneumonia (IIP) that exhibited skin ulcers due to increased heparin precipitable fraction (HPF) in plasma. This case prompted us to investigate the occurrence and significance of HPF in interstitial pneumonia (IP). The subjects included patients with IIP (acute exacerbation 6 cases, chronic active stage 12 cases), IP associated with collagen vascular disease (CVD) (9 cases) and granulomatous lung diseases (7 cases). The data indicated that all of the cases with acute exacerbation of IIP exhibited increased plasma HPF values (218-951 mg/dl) compared to those of normal controls (less than 180 mg/dl). In contrast, the values ranged within normal limits in all of the cases with IP associated with CVD. In a companion study, we measured plasma HPF values in patients with lung cancer, bacterial pneumonia and diffuse panbronchiolitis. It was found that 22% of the subjects showed increased plasma HPF values. We also investigated whether there were correlations between plasma HPF and various inflammatory parameters. The data revealed that there were correlations between HPF and ESR, CRP, alpha 1-globulin, alpha 2-globulin, complement (C3) or fibrinogen. However, there was no correlation between HPF and fibronection. These results suggest that plasma HPF is valuable to evaluate the acute exacerbation of IIP, although the elevation of plasma HPF levels is not specific.     

The role of bronchoalveolar lavage in interstitial lung disease

Considerable progress has been made in understanding the similarities and differences among the forms of the interstitial lung diseases (ILDs), particularly the forms of idiopathic interstitial pneumonia, now recognized as distinct clinicopathologic entities. Lung parenchymal evaluation by high-resolution CT scanning of the chest may provide images that are virtually diagnostic of certain forms of ILD, but other testing, including bronchoalveolar lavage (BAL) and lung biopsy, may be required for accurate diagnosis. The differential diagnosis of these disorders rests on the clinician's interpretation of the clinical presentation and physical examination findings, pulmonary function testing, radiographic imaging, and, if required, sampling of lung tissue. This discussion examines the usefulness of BAL in the diagnosis of specific forms of ILD.     

Studies on the pathogenesis of lung fibrosis by bronchoalveolar lavage and Ga scintigraphy

The pathogenesis of lung fibrosis in patients with idiopathic interstitial pneumonia (IIP) and other interstitial pneumonia was studied with bronchoalveolar lavage (BAL) and gallium (Ga) scintigraphy. Patients with interstitial pneumonia showed increased populations of lymphocytes, neutrophils and basophils (mast cells) in BAL fluids especially in patients is the active stage of interstitial pneumonia. Fibronectin concentration in BAL fluids of patients with interstitial pneumonia was higher than those of normal control. These fibronectin levels in BAL fluids were shown to correlate with the density of total cell, macrophage and neutrophil in each BAL fluid. Enhanced fibronectin synthesis by alveolar macrophages in vitro was observed in patients with IIP in comparison with that of normal control. Increased Ga radioactivity was shown in BAL fluids of patients with interstitial pneumonia right after the Ga scintigraphy. The Ga index (Ga in BAL fluid/Ga in peripheral blood) correlated with the density of total cell and macrophage in BAL fluid. These data indicate that the accumulation of activated alveolar macrophages and neutrophils could play an important role in the pathogenesis of lung fibrosis in patients with interstitial pneumonia.     

The role of interleukin-8 in interstitial pneumonia

OBJECTIVE: A variety of inflammatory cells accumulate in the lungs of patients with interstitial lung disease. The potential for IL-8 to be released from these cells into the lungs of patients with idiopathic interstitial pneumonia (IIP), interstitial pneumonia with collagen vascular disease (IP-CVD), sarcoidosis (SAR) and hypersensitivity pneumonitis (HP) was investigated. METHODOLOGY: IL-8 levels were assessed by enzyme-linked immunosorbent assay in BAL fluid and serum, and the expression of IL-8 in the lungs of these patients was evaluated by immunohistochemistry. RESULTS: Serum IL-8 levels were significantly elevated in patients with IIP (P < 0.05) and SAR (P < 0.01). In BAL fluid, the IL-8 level was significantly higher in patients with IIP (P < 0.05), IP-CVD (P < 0.01), SAR (P < 0.01) and HP (P < 0.01). In several cases, IL-8 level correlated with neutrophil density. The IL-8 immunopositive cells were type II pulmonary epithelial cells and alveolar and interstitial macrophages in patients with IIP and IP-CVD. CONCLUSIONS: IL-8 is likely to be a key factor in the pathogenesis of fibrosis of the lung and in lung injury.     

A prospective study of idiopathic interstitial pneumonia and collagen vascular disease preceded by interstitial pneumonia

The incidence and latency period of collagen vascular disease (CVD) were surveyed prospectively in patients originally diagnosed as idiopathic interstitial pneumonia (IIP). We also examined whether there were differences between IIP and CVD preceded by interstitial pneumonia. Background information, extrapulmonary symptoms, smoking history, laboratory findings, prognosis (Kaplan-Meier estimates), respiratory functions, and radiological findings were compared. The subjects consisted of 68 patients of whom 13 (19%) developed CVD (RA; 5 cases, DMPM; 5 cases, SLE; 1 case, Sjoegren syndrome; 1 case, Overlap syndrome; 1 case). The latency period for development of CVD was 24.9 +/- 39.2 (mean +/- SD) months. IIP patients who developed CVD were predominantly female and were younger than those without CVD (p less than 0.05). These patients also had faster ESR, higher CPK values, and a higher incidence of arthralgia, joint deformity and clubbed fingers (p less than 0.05). Abnormal shadows around costo-phrenic angles were seen more frequently in patients with CVD (p less than 0.05). These results suggest that quite a number of patients with IIP develop CVD. The clinical course of these patients should be followed by keeping these clinical findings in mind.     

Smoking-related interstitial lung diseases

Interstitial lung diseases (ILDs) encompass diverse clinicopathological disease entities ranging from idiopathic interstitial pneumonia (IIP) to interstitial pneumonia accompanied by collagen vascular diseases and diseases related to smoking, drug reactions, occupational environments, infections, and malignancies. Our focus is on the smoking-related interstitial lung diseases. Specifically, we focus on reports suggesting that chronic smoking is deeply involved in the disease pathogenesis and on reports suggesting that chronic smoking may influence the clinical course in terms of either disease severity or progression. Pulmonary Langerhans' cell granulomatosis (PLCG), desquamative interstitial pneumonia (DIP), respiratory bronchiolitis with interstitial lung diseases (RB-ILD), interstitial pneumonia associated with rheumatoid arthritis, acute respiratory distress syndrome (ARDS), and idiopathic pulmonary fibrosis (IPF) are covered.     

Lung transplantation in IIP: A review

The idiopathic interstitial pneumonias (IIP) encompass a large and diverse subtype of interstitial lung disease (ILD) with idiopathic pulmonary fibrosis (IPF) and non‐specific interstitial pneumonia (NSIP) being the most common types. Although pharmacologic treatments are available for most types of IIP, many patients progress to advanced lung disease and require lung transplantation. Close monitoring with serial functional and radiographic tests for disease progression coupled with early referral for lung transplantation are of great importance in the management of patients with IIP. Both single and bilateral lung transplantation are acceptable procedures for IIP. Procedure selection is a complex decision influenced by multiple factors related to patient, donor and transplant centre. While single lung transplant may reduce waitlist time and mortality, the long‐term outcomes after bilateral lung transplantation may be slightly superior. There are numerous complications following lung transplantation including primary graft dysfunction, chronic lung allograft dysfunction (CLAD), infections, gastroesophageal reflux disease (GERD) and airway disease that limit post‐transplant longevity. The median survival after lung transplantation is 4.7 years in patients with ILD, which is less than in patients with other underlying lung diseases. Although long‐term survival is limited, this intervention still conveys a survival benefit and improved quality of life in suitable IIP patients with advanced lung disease and chronic hypoxemic respiratory failure.     

Unique characteristics of systemic sclerosis sine scleroderma-associated interstitial lung disease

STUDY OBJECTIVES: To describe the characteristics of systemic sclerosis sine scleroderma (ssSSc)-associated interstitial lung disease (ILD) presenting as idiopathic interstitial pneumonia (IIP). DESIGN: Retrospective review of six patients with ssSSc-associated ILD diagnosed after referral for evaluation of IIP. MEASUREMENT AND RESULTS: All patients were white, their mean age was 56 years (range, 37 to 86), and gender was evenly divided. Sclerodactyly, skin thickening, and digital edema were absent in all patients. All patients had scattered telangiectasia, and four patients had Raynaud phenomenon with abnormal nailfold capillaroscopy findings. All described gastroesophageal reflux, and three patients had esophageal dysmotility by esophagography. All had restrictive pulmonary physiology and a reduced diffusion capacity. High-resolution CT revealed nonspecific interstitial pneumonia (NSIP) or usual interstitial pneumonia (UIP) radiographic patterns. Of the three patients who underwent surgical lung biopsy, two patients had NSIP and one patient had UIP pathologic patterns. Five patients had asymptomatic pericardial effusions and elevated pulmonary artery pressures by echocardiography. All patients had nucleolar-staining anti-nuclear antibodies (ANAs), and one patient was anti-Scl-70 positive. All five anti-Scl-70-negative patients were anti-Th/To positive, and the anti-Scl-70-positive patient was anti-Th/To negative. CONCLUSIONS: In the presentation of an IIP, the presence of a nucleolar-staining ANA, telangiectasia, Raynaud phenomenon with abnormal capillaroscopy findings, gastroesophageal reflux, or pericardial disease suggests underlying systemic sclerosis. These findings should aid clinicians in the evaluation and treatment of patients with otherwise undefined ILD.     

Comparison of bronchoalveolar lavage fluids from nonspecific interstitial pneumonia and from ordinary interstitial pneumonia]

We studied cell findings in the bronchoalveolar lavage fluid (BALF) of 13 patients with nonspecific interstitial pneumonia (NSIP) and 20 with ordinary interstitial pneumonia (UIP). NSIP and UIP were difficult to distinguish by high-resolution CT. Surgical lung biopsies were performed in all patients. We divided the patients with NSIP and UIP into 4 groups, a group of idiopathic NSIP (idiopathic NSIP), a group of NSIP patients associated with collagen vascular disease (CVD NSIP), a group of idiopathic UIP patients (idiopathic UIP) and a group of UIP patients associated with collagen vascular disease (CVD UIP). We then examined the differences in BALF cell findings between these groups. The percentage of lymphocytes in BALF was higher in idiopathic NSIP and CVD NSIP than in the healthy control. The percentage of alveolar macrophages was lower and the percentage of lymphocytes was higher in CVD NSIP than in idiopathic UIP. The CD4/CD8 ratio in BALF of idiopathic NSIP was lower than with idiopathic UIP. It is important that NSIP be distinguished from UIP clinically, and our results suggest that BALF cell findings may be useful for making this distinction.     

A comparative study of the prognosis for Japanese patients with idiopathic interstitial pneumonia or BOOP based on histopathologic subsets]

We explored the prognosis for 123 patients with either idiopathic interstitial pneumonia (IIP) or bronchiolitis obliterans organizing pneumonia (BOOP). All patients underwent either open lung biopsy or thoracoscopic lung biopsy procedures. The histopathologic diagnosis of IIP included patients with usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), and desquamative interstitial pneumonia with respiratory bronchiolitis-associated interstitial lung disease. The prognosis was poorest for patients with a histologic diagnosis of UIP, and excellent for those who received a diagnosis of BOOP. Although the prognosis is generally considered to be good for patients with NSIP, some NSIP patients in our study died. Histopathologic diagnosis based on surgical lung biopsy is useful in evaluating the prognosis for patients with IIP.