Idiopathic Interstitial Pneumonia Patients Research Articles

Evaluation of the elastase burden in patients with idiopathic interstitial pneumonia

This study was designed to clarify the role of neutrophil elastase in the pathogenesis of idiopathic interstitial pneumonia (IIP). To accomplish this, elastase: alpha 1-antitrypsin complexes in plasma and bronchoalveolar lavage fluids (BALF) were measured in 19 patients with IIP and compared to 15 normal smokers. Cell differentiation counts showed that there was no difference in percent neutrophils in BALF between IIP patients and normal smokers. However, elastase: alpha 1-antitrypsin complexes were significantly increased in both plasma and BALF in patients with IIP compared to normal smokers. In IIP patients with honeycombing demonstrated by high resolution CT, although elastase: alpha 1-antitrypsin complexes were not significantly increased in plasma, elastase: alpha-antitrypsin complexes in BALF were significantly increased compared to IIP patients without honeycombing. Western immunoblot analysis showed that although the native 80-KD elastase: alpha-antitrypsin complex was detected in BALF, the molecular weight of elastase: alpha 1-antitrypsin complex in plasma was 60-KD.

Incidence and clinical features of lung cancer in patients with idiopathic interstitial pneumonia

We studied the incidence of lung cancer in the 599 patients with idiopathic interstitial pneumonia (IIP) who had visited to 37 institutions during 1991. In addition to 89 patients with lung cancer registered initially 29 were found during more than 4 years of follow-up, which indicates that annual incidence of lung cancer in these patients with IIP was a few percent. A total of 118 lung cancers accounted for 19.7% of all the IIP patients registered and also for 27.2% of the 435 IIP patients in whom a definite outcome was certified by this study. Most of the patients with lung cancer were older men who were heavy smokers. The distribution of histological types was not noteworthy. On the chest rentgenogrms, the tumors were found predominantly in the peripheral lung fields even in the patients with squamous cell cancer, but no apparent association with IIP lesion was observed. Surgical resection was done in only 52% of the patients with the disease at stage I or II; chemotherapy and/or radiotherapy were given to 52.4% of the patients with advanced disease, which may have been due to considerations of the adverse effects of anticancer treatment on the prognoses. The mortality in IIP patients with lung cancer was higher than in those without lung cancer, mainly due to progression of the lung cancer, not the IIP. This indicates the importance of lung cancer as a prognostic factor in patients with IIP.

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.

Clinical criteria for definition of idiopathic interstitial pneumonia (IIP)

Clinical criteria for definition of IIP proposed in 1991 by the Project Team for Diffuse Lung Diseases Organized by Japanese Ministry of Health and Welfare are reviewed. After the clinical roentgenological, and pathological researches of 92 IIP patients, we concluded that IIP patients were grouped into two clinical types, acute and chronic, by their clinical courses and characteristic pathological findings. The latter is, moreover, grouped into two types, typical and atypical, by their morphological characteristics. The acute type are represented by alveolitis with marked edema and cell infiltration of alveolar wall, and by hyaline membrane formation. "Typical" of chronic types only have typical pathologic changes of interstitial pneumonia and/or fibrosis represented by honeycombing. "Atypical" have both those interstitial changes and intra-alveolar scar formation and fibrosis due to organized pneumonia and secondarily occurred emphysema such as bulla as well. The continuity in clinical courses between acute and chronic types are still obscure.

Lung cancer associated with idiopathic interstitial pneumonia

Idiopathic interstitial pneumonia (IIP) is known to have a tendency to be associated with lung cancer. Clinical characteristics of lung cancer associated with IIP are discussed in this article. Thirteen cases of lung cancer associated with IIP were examined from 1975 to 1988. A total of 590 cases of lung cancer and 38 cases of IIP were observed during that period. The 13 cases of lung cancer were found to be associated with IIP during the follow-up observation of our patients. Of these 13 patients, 12 men and a woman, the average age was 68.0 years old. All these 13 cases were ex- or present smokers. Five cases of lung cancer had no symptoms, but were detected by abnormal shadows on chest X-ray. Eight cases were detected symptoms. The duration from the onset of IIP to the onset of lung cancer was 36.5 +/- 23.5 months. Primary sites of lung cancer were distributed as follows. Nine cancers were in the left lung (64%) and five cancers were in the right lung (36%). Three cancers were in the hilar region (21%) and 11 cancers were in the peripheral lung field (79%). The numbers of lung cancers were equal in upper and lower lobe. The most common histological type was squamous cell carcinoma, followed by adenocarcinoma. Most cases were in stage III or IV. Three cases were operated, 4 were treated with chemotherapy, 4 were treated with chemotherapy plus irradiation, and 2 cases were treated by BRMs. The frequency of weight loss or finger clubbing in these patients was higher than in IIP patients without lung cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

A prospective study of lung cancer in cases of idiopathic interstitial pneumonia (IIP)

The incidence of lung cancer in 45 patients (37 males and 8 females), who were originally diagnosed as having idiopathic interstitial pneumonia (IIP), was studied prospectively by following them 4 to 10 years. As controls, sex-, age-, and smoking history matched patients with chronic obstructive lung disease (COLD) were also surveyed for the same follow up period. In addition, the differences in clinical findings between those with and without lung cancer were examined. Eight out of 45 patients with IIP (18%) developed lung cancer (adenocarcinoma; 4, small cell carcinoma; 3, squamous cell carcinoma; 2, including one double cancer). All lung cancer patients were male smokers. Looking only at males, 8 out of 37 patients with IIP (21.6%) developed lung cancer. This incidence was significantly higher than that of the male COLD group (2.2%, less than 0.01). In clinical findings, IIP patients with lung cancer had the characteristics of the chronic type of IIP (lack of volume loss on chest radiographic milder dyspnea, not on steroid treatment) when compared with those who did not develop lung cancer.

Complications of lung biopsy in patients with idiopathic interstitial pneumonia and risk factors thereof

To investigate the complication rate of lung biopsy in patients with idiopathic interstitial pneumonia (IIP) and the risk factors thereof. The clinical data of 66 IIP patients underwent lung biopsy were analyzed. Of the 66 patients, 21 undergoing surgical lung biopsy (SLB) including open lung biopsy (OLB) (n = 11) and video-assisted thoracic surgery (VATS) (n = 10), and 45 patients undergoing biopsy other than SLB, including transbronchial lung biopsy (TBLB, n = 28) and CT or B mode ultrasonography-guided percutaneous transthoracic needle lung biopsy (n = 17). The general postoperative complication rate was 40.9% (27/66), and the postoperative complication rate was 71.4% (15/21) in the SLB group, significantly higher than that of the non-SLB group (26.7%, 12/45, chi2 = 4.55, P = 0.03). The complications of the SLB group included prolonged air leakage (n = 10, 47.6%), pleural effusion (n = 5, 23.8%), acute pulmonary edema (n = 5, 23.8%), and postoperative pulmonary infection (n = 4, 19.0%), and the complications of the non-SLB group included pneumothorax after percutaneous transthoracic lung needle biopsy or TBLB (n = 12, 26.7%), acute exacerbation (AE) (n = 2, 4.4%), respiratory failure requiring mechanical ventilation for more than 72 h (n = 1, 2.2%), and postoperative pulmonary infection (n = 1, 2.2%). The predicted diffusing capacity of the lings for carbon monoxide (DLCO%) of the SLB group patients with postoperative complications was (46. 83 +/- 17.01)%, significantly higher than that of the SLB group patients without postoperative complication [(75.93 +/- 25.62)%, t = 2.55, P = 0.02]. However, there were not significant differences in the lung function and blood gas indexes among the patients undergoing different procedures of lung biopsy, with and without postoperative complications. Six of the 66 patents died within 90 postoperative days with a mortality of 9.1%, the causes of death of 3 of which were associated with lung biopsy. The IIP patients undergoing SLB suffer from more postoperative complications than those undergoing other lung biopsy procedures with the lower DLCO% as the probable associated factor. AE in the IIP patients can be induced by CT-guided percutaneous transthoracic needle lung biopsy and TBLB, and results in death.

A 55-year-old craftsman with dyspnea and clubbing: a case report

IntroductionClubbing is very uncommon in respiratory bronchiolitis-associated interstitial lung disease, and primarily raises the suspicion of idiopathic pulmonary fibrosis in a patient presenting with diffuse parenchymal lung disease. If idiopathic pulmonary fibrosis can be excluded, clubbing should raise the suspicion of an occult tumour.Case presentationWe describe a heavy smoker presenting with dyspnea and severe clubbing. Surgical lung biopsy revealed the histologic diagnosis of respiratory bronchiolitis-associated interstitial lung disease. Respiratory bronchiolitis-associated interstitial lung disease is a distinct clinicopathologic entity within idiopathic interstitial pneumonia patients described almost exclusively in cigarette smokers. The disease is associated with a good prognosis and mild symptoms but not with clubbing. After smoking cessation the radiologic findings of interstitial lung disease improved in parallel with improvement in lung function and gas exchange. However, a central squamous cell carcinoma was detected in the follow-up.ConclusionIn this case, clubbing was most probably caused by the occult tumor rather than by respiratory bronchiolitis-associated interstitial lung disease.

Short telomeres are a risk factor for idiopathic pulmonary fibrosis

Idiopathic interstitial pneumonias (IIPs) have a progressive and often fatal course, and their enigmatic etiology has complicated approaches to effective therapies. Idiopathic pulmonary fibrosis (IPF) is the most common of IIPs and shares with IIPs an increased incidence with age and unexplained scarring in the lung. Short telomeres limit tissue renewal capacity in the lung and germ-line mutations in telomerase components, hTERT and hTR, underlie inheritance in a subset of families with IPF. To examine the hypothesis that short telomeres contribute to disease risk in sporadic IIPs, we recruited patients who have no family history and examined telomere length in leukocytes and in alveolar cells. To screen for mutations, we sequenced hTERT and hTR. We also reviewed the cases for features of a telomere syndrome. IIP patients had shorter leukocyte telomeres than age-matched controls (P < 0.0001). In a subset (10%), IIP patients had telomere lengths below the first percentile for their age. Similar to familial cases with mutations, IPF patients had short telomeres in alveolar epithelial cells (P < 0.0001). Although telomerase mutations were rare, detected in 1 of 100 patients, we identified a cluster of individuals (3%) with IPF and cryptogenic liver cirrhosis, another feature of a telomere syndrome. Short telomeres are thus a signature in IIPs and likely play a role in their age-related onset. The clustering of cryptogenic liver cirrhosis with IPF suggests that the telomere shortening we identify has consequences and can contribute to what appears clinically as idiopathic progressive organ failure in the lung and the liver.

Anti-endothelial cell antibodies in patients with interstitial lung diseases

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. 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). 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. 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.

Incidence of Pulmonary Hypertension and Its Clinical Relevance in Patients with Interstitial Pneumonias: Comparison between Idiopathic and Collagen Vascular Disease Associated Interstitial Pneumonias

This study was undertaken to investigate the frequency of pulmonary hypertension (PH), and clinical parameters associated with PH in patients with idiopathic interstitial pneumonias (IIPs) and collagen vascular disease-associated interstitial pneumonias (CVD-IPs). Retrospective analyses were performed in 163 consecutively enrolled patients (78 IIPs and 85 CVD-IPs) who were being evaluated for PH by Doppler echocardiography. PH was defined as an estimated systolic pulmonary artery pressure (sPAP) of > or = 40 mmHg. The frequency of PH was evaluated and clinical parameters were compared between patients with PH and those without PH. Among patients successfully evaluated for sPAP by echocardiography, 20 of 70 (28%) patients with IIPs and 17 of 80 (21%) patients with CVD-IPs had PH. Among patients with IIP and CVD-IP, those with PH were more frequently treated with supplemental oxygen. Patients with IIP who had PH tended to be older and had decreased % diffusion capacity of carbon monoxide (%DLCO). Additionally, in patients with IIP, sPAP was negatively correlated with %DLCO. However, this association was not found in patients with CVD-IP. Patients with CVD-IP who had PH were predominantly male. PH was frequently observed in patients with both IIPs (28%) and CVD-IPs (21%) in the chronic phase of the disease. PH should be evaluated in patients with IPs who need supplemental oxygen, IIP patients with decreased diffusing capacity, and in patients with CVD-IP.

Serum CC-10 in Inflammatory Lung Diseases

Background: Although Clara cell secretory protein (CC-10) has been ascribed an anti-inflammatory role in lung diseases, its precise role remains unclear. Objective: To further our understanding of the role of CC-10 in inflammatory lung diseases, CC-10 protein levels were measured. Methods: Sera or bronchoalveolar lavage (BAL) fluids were collected from patients with different inflammatory lung diseases including bronchial asthma, chronic obstructive lung disease (COPD), sarcoidosis, idiopathic interstitial pneumonia (IIP), chronic eosinophilic pneumonia (CEP), pneumonia and lung cancer. Serum CC-10 concentrations were measured by enzyme-linked immunosorbent assay using urinary protein-1 antibody. Then, the relationships between CC-10 concentrations and lung diseases were investigated. Immunohistochemistry was performed using lung biopsy samples. Results: Increased serum CC-10 levels were recognized in IIP patients, while CC-10 levels were decreased in bronchial asthma patients and CEP patients. Immunohistochemistry revealed an aberrant expression in areas of fibrosis in IIP patients. Serum CC-10 concentrations were not associated with severity among IIP, COPD, and sarcoidosis. In contrast, serum CC-10 concentrations were correlated with FEV₁/FVC in bronchial asthma patients. Conclusions: Although the number of patients was quite limited, these data provide new insights into the role of CC-10 in lung diseases, and the possibility that the CC-10 concentration in serum could be a new marker indicating the severity of bronchial asthma.

Human Pulmonary Fibroblasts Exhibit Altered Interleukin-4 and Interleukin-13 Receptor Subunit Expression in Idiopathic Interstitial Pneumonia

Abnormal proliferation of pulmonary fibroblasts is a prominent feature of chronic pulmonary fibrotic diseases such as idiopathic interstitial pneumonia (IIP), but it is not presently clear how this proliferative response by lung fibroblasts can be therapeutically modulated. In the present study, we examined whether it was possible to selectively target primary human pulmonary fibroblasts grown out of surgical lung biopsies (SLBs) from IIP patients based on their expression of interleukin-4 receptor (IL-4R) and IL-13R subunits. Pulmonary fibroblast lines cultured from patients with the severest form of IIP, namely usual interstitial pneumonia, exhibited the greatest gene and protein expression of IL-4Ralpha, IL-13Ralpha1, and IL-13Ralpha2 compared with primary pulmonary fibroblast lines grown from other IIP SLBs and normal SLBs. When exposed to increasing concentrations of a chimeric protein comprised of human IL-13 and a truncated version of Pseudomonas exotoxin (IL13-PE), the proliferation of primary usual interstitial pneumonia fibroblasts was inhibited to a much greater extent compared with fibroblast lines from nonspecific interstitial pneumonia and respiratory bronchiolitis/interstitial lung disease patient groups. Fibroblasts from normal patients exhibited minimal susceptibility to the cytotoxic effect of IL13-PE. IL13-PE-mediated targeting of IIP fibroblasts was dependent on their expression of IL-4Ralpha and IL-13Ralpha2. Thus, these data suggest that the abnormal proliferative properties of human lung fibroblasts from certain IIP patient groups can be modulated in a manner that is dependent on the IL-4 and IL-13 receptor subunit expression by these cells.

Therapeutic Targeting of IL-4- and IL-13-Responsive Cells in Pulmonary Fibrosis

Severe forms of idiopathic interstitial pneumonia (IIP), such as usual interstitial pneumonia (UIP), can be impervious to modern steroid and immunosuppressive treatment regimens, thereby emphasizing the need for novel effective therapies. Understanding the cytokine networks that may affect immune and structural cell activation and, hence, the progression of these fatal fibrotic diseases, has been a focus in our research. In this regard, we have examined the role of interleukin (IL)-4 and IL-13 and their respective receptor subunits in this process. Examination of clinical surgical lung biopsies (SLBs) showed that IIP is characterized by the abnormal, heightened expression of the receptor subunits that bind IL-4 and IL-13. Specifically, IL-4Ralpha and IL-13Ralpha2 (the high-affinity IL-13 receptor subunit) was present in greater abundance in SLBs and fibroblasts from IIP patients compared with normal patients, who exhibited no evidence of pulmonary fibrosis. These clinical findings prompted us to investigate whether the targeting of pulmonary cell types that were highly responsive to IL-4 and IL-13 was a viable therapeutic option in IIP. Using a chimeric protein comprised of human IL-13 and a truncated version of an exotoxin from Pseudomonas (abbreviated IL13-PE), we observed that IL13-PE selectively targeted human pulmonary fibroblasts grown from IIP SLBs, whereas it had a minimal effect on fibroblasts grown from biopsies from normal patients. In murine models characterized by abnormal airway or interstitial fibrotic responses, the intranasal administration of IL13-PE significantly attenuated the fibrotic response through the targeting of IL-4Ralpha- and IL-13Ralpha2-expressing pulmonary cells, including monocytes, macrophages, and pulmonary fibroblasts. Together, these data demonstrate that IL-4 and IL-13 are required for the initiation and maintenance of pulmonary fibrosis, and highlight the importance of further investigation of anti-fibrotic therapeutics that prevent the action of both cytokines during clinical pulmonary fibrosis.

Steroid treatment based on the findings of transbronchial biopsy in idiopathic interstitial pneumonia.

This study was performed to find the rationale for administering steroids to patients with idiopathic interstitial pneumonia (IIP), which was unlikely to be usual interstitial pneumonia (UIP) but was not surgically biopsied. Among IIP patients in the file of the departments, nine patients who met the following criteria were selected for this study ("non-UIP" group): 1) transbronchial lung biopsy showed dense mononuclear cell infiltration in thickened alveolar septa; 2) chest radiograph and computed tomography showed irregular linear, reticular or ground-glass opacities with alveolar consolidation without honeycombing in the lung base; and 3) spirometry was performed before and after steroid therapy. Ten patients with pathologically confirmed nonspecific interstitial pneumonia ("NSIP" group) were also selected for the comparison. Baseline values and percentage increase of vital capacity (VC) after steroid therapy were plotted. Steroids improved VC in both groups of patients. After 1 yr of steroid therapy, percentage increase of VC in "non-UIP" was 28.8+/-7.7%, which was not significantly different from that in NSIP (30.0+/-11.7%). One "non-UIP" patient and one NSIP patient died after 6.4 and 4.3 yrs of follow-up, respectively. Patients with idiopathic interstitial pneumonia presenting cellular interstitial pneumonia in transbronchial lung biopsy, in addition to radiographic findings not typical for usual interstitial pneumonia, could expect a beneficial effect of steroids without undergoing surgical biopsy.

The Relationship of Serum Angiotensin Converting Enzyme (ACE), Angiotensin II and Clinical Markers in the Idiopathic Interstitial Pneumonia

Background : There have been several studies showing that angiotensin II and the angiotensin converting enzyme (ACE) contribute to the activation of fibroblast including the pulmonary fibrosis, and apoptosis of the alveolar epithelium in idiopathic intersititial pneumonia. This study was performed to identify the relationship between the serum angiotensin II, ACE and the pulmonary function test (PFT), the dyspnea score, and the cell fraction of the bronchoalveolar lavage fluid(BALF). Materials and Methods : Twenty three patients with idiopathic interstitial pneumonia from March, 1999 to October, 2001 at Gachon medical school were enrolled in this study. They were divided into IPF(UIP) (16) and NSIP (7) groups. Twelve of the idiopathic interstitial pneumonia patients (UIP : 5, NSIP : 7) were diagnosed by an open lung biopsy, 11 of IPF patients were diagnosed by the American Thoracic Society (ATS) diagnostic criteria. The PFT values, dyspnea score, serum ACE and angiotensin II were measured, and a bronchoscopy was performed to obtain the BALF. Results : Of all the patients, 7 were in the normal range and 14 showed an increase in the serum level of angiotensin II. In terms of the serum ACE level, 14 patients had an increased level. The DLCO% of the angiotensin II in increased group was significantly lower than the not-increased group (p=0.021). Other factors did not correlate with the serum ACE or the angiotensin II increased group and not-increased group. Conclusion : These results suggest that an increased angiotensin II serum level may be associated with increase in the of alveolar capillary block in the progression of pulmonary fibrosis in idiopathic interstitial pneumonia.

Clinical characteristics of idiopathic interstitial pneumonia (IIP) with bullae.

Multiple bullae have often been observed in the lungs of patients with idiopathic interstitial pneumonia (IIP). The etiology of bullae has been considered to be distinct from that of interstitial pneumonia and honeycomb lesions seen in IIP. The incidence of bullae was evaluated in 27 IIP patients (male; 23 cases, female; 4 cases) and clinical factors which are related to the development of bulla were analyzed. Of the 27 patients, 16 (59%) had bullae. All 16 were male smokers, and had higher smoking indices (p < 0.01) than patients without bullae. Eleven of the 16 IIP patients with bullae had clubbed fingers (69%, p < 0.05). Roentgenologically, cysts (75%, p < 0.05), low attenuation area (56%, p = 0.06), and honeycomb appearance (94%, p = 0.07) were observed more often in IIP patients with bullae. These results suggest that smoking habits may have a close relationship to the development of bullae seen in patients with IIP.

Pathogenesis of development of lung cancer in idiopathic interstitial pneumonia--growth factors in bronchoalveolar lavage fluid

It has been generally accepted that lung fibrosis as in idiopathic interstitial pneumonia (IIP) is frequently associated with the development of lung cancer. This observation implies that the mechanism involved in carcinogenesis and/or enhanced proliferation of cancer cells is common to the fibrosing process. However, there are few studies reported on the pathogenesis of associated lung cancer except for several studies assessed from the point of view of surgical pathology. This study was undertaken to learn whether BAL fluid, which reflects the local milieu of the fibrosing process, enhances the proliferation of human lung cancer cell line Lu-99, Lu-65 and rat lung fibroblasts as assessed by 3H-thymidine incorporation. BAL fluid was obtained from patients with IIP (n = 8) and normal volunteers (n = 8). BAL fluids from patients with IIP enhanced the mean incorporation of 3H-thymidine of Lu-99 up to 3.6 times (p < 0.01) compared to that of normal volunteers. Furthermore, the mean incorporation of Lu-65 was increased up to 1.8 times (p < 0.05) by BAL fluids from patients with IIP. In contrast, BAL fluids from patients caused no significant increase of the mean incorporation of rat lung fibroblasts as compared to normal BAL fluids. The enhancing activities on the growth of cancer cell line Lu-99, Lu-65 were eluted in several fractions by high performance liquid chromatography using Superose 12. These observations indicate that the BAL fluid of IIP patients contains factors enhancing the growth of cancer cells.

QUANTITATIVE ANALYSIS BY PARTICLE INDUCED X- RAY EMISSION (PIXE) OF TRACE ELEMENTS IN LUNG TISSUE OF IDIOPATHIC INTERSTITIAL PNEUMONIA PATIENT

It has been previously shown that activated alveolar macrophage in idiopathic interstitial pneumonia (IIP) played an important role in the process of fibrosing, but the initial agent which activates alveolar macrophages has not been proved. The present study was designed to make quantitative analyses of trace elements in the lung tissue speciments of IIP patients and normal controls. Particle induced X-ray emission (PIXE) was used. The IIP group consisted of 11 patients and the Control group, which had no apparent history for dust inhalation and lung diseases, consisted of 9 subjects. More silicon and magnesium were found in the IIP group than in the normal controls. These data suggested that inhalation of silicon and magnesium might be one of the etiologic factors of IIP.

SURGERY OF GASTRIC CANCER IN 3 PATIENTS WITH IDIOPATHIC INTERSTITIAL PNEUMONIA

Diffuse interstitial pneumonia of unknown etiology which carries a poor prognosis is designated idiopathic interstitial pneumonia (IIP) in Japan. Since IIP can suddenly exacerbate for unknown cause, meticulous care must be exercised in its surgical treatment.Recently we performed surgery on three IIP patients for gastric cancer. One of them experienced acute exacerbation. This patient was old, aged 74 years, and was in a much poorer respiratory condition than other patients before surgery. Since the patient had a progressive cancer in the pyloric region, subtotal gastrectomy was performed under general anesthesia. On the second postoperative day acute exacerbation was noted. The patient was placed on high-dose steroid therapy under artificial respiratory control, but died on the 18th postoperative day.Our experience in the case suggests that, to prevent acute exacerbation of IIP, it is advisable to improve the respiratory condition of the patient to the greatest possible extent, reduce the load on the respiratory system during surgery, and provide sufficient ventilation after surgery.