Pulmonary Blood- and Extravascular Water Volumes during Prolonged Post-Hemorrhagic Systemic Hypotension

In cats prolonged hemorrhagic hypotension had been shown to increase the pulmonary arterial pressure and vascular resistance. Pulmonary extravascular water volume and pulmonary blood volume have been evaluated early and late in such a period of post-hemorrhagic hypotension. ⁵¹Cr-labelled erythrocytes and ¹²⁵I-labelled albumin were injected intravascularly to animals with an opened chest and on positive pressure ventilation. One upper lung lobe was then suddenly clamped, removed and frozen. The lung lobe tissue and a simultaneously taken blood sample from a large vessel were measured for total w-eight, dry weight and tracer content. The lobe's blood volume and extravascular water volume were then calculated per unit extravascular lung dry weight. A second lung lobe was removed and treated similarly at a later stage. 1 /2 h after the blood loss there was a marked reduction in lung blood volume and at the same time some increase in pulmonary extravascular water volume indicating constriction of postcapillary capacitance vessels. After 3 h of hypotension pulmonary extravascular water volume was found to be the same as before the hemorrhage although the pulmonary arterial pressure increased. This indicated that the increase in vascular resistance must predominantly be due to vasoconstriction at precapillary sites. The reduction in the lungs' blood volume remained at these late stages indicating that capacitance vessels were still constricted. When hyperinflations of the lungs were omitted in the experimental period, there was a tendency towards water accumulation in the lungs.     

Normal chest roentgenograms in chronic diffuse infiltrative lung disease

We undertook this study to determine the prevalence of normal roentgenograms in chronic diffuse infiltrative lung diseases. Of 458 patients with such disorders histologically confirmed, 44, or 9.6 per cent, had normal pre-biopsy films. In this group with normal x-ray films, desquamative interstitial pneumonia, sarcoidosis and allergic alveolitis were the most frequent diagnoses. Dyspnea was the principal complaint, and fine rales were common. The vital capacity was reduced in 57 per cent, and the single-breath diffusing capacity in 71 per cent. In half, histological changes and functional impairment were moderately severe. Films may be normal in such cases because isolated foci are too small or too few, because diffuse interstitial or intra-alveolar disease may cast no discrete shadows or because the lesions primarily affect airways or blood vessels. Patients with normal chest roentgenograms and normal mechanics of breathing but with impaired gas exchange should have lung biopsy for early diagnosis and therapy.     

Reference values for pulmonary tissue volume, membrane diffusing capacity, and pulmonary capillary blood volume

Pulmonary tissue volume (Vti), carbon monoxide diffusing capacity, membrane diffusing capacity, pulmonary capillary blood flow and pulmonary capillary blood volume were measured in ninety (54 men and 36 women) healthy lifetime nonsmokers using an inert gas rebreathing technique. Prediction equations were generated using multiple linear regressions with height and age as the independent variables. Normalizing the data by dividing by functional residual capacity eliminated all sex differences. In contrast to the other variables, normalized pulmonary tissue volume did not correlate with any of the independent variables tested. Therefore, an average normalized Vti value can be recommended as a reference value     

Role of small airways in asthma: investigation using high-resolution computed tomography

BACKGROUND: Small airways may have an important role in asthma but are more difficult to assess pathologically than central airways. Computed tomographic indices of lung density are assumed to reflect air trapping and may be a useful noninvasive measure of small airways disease, but their pathophysiological relevance remains undetermined. OBJECTIVE: To evaluate lung density on high-resolution computed tomography and examine its correlations with clinical and physiologic variables in 29 patients with stable asthma. METHODS: Both lungs were scanned at full-inspiratory and full-expiratory phases to quantify percentage of lung field occupied by low attenuation area (LAA%; < -960 Hounsfield units) and mean lung density. Asthma severity, pulmonary function, methacholine airway sensitivity and reactivity, and sputum eosinophil counts were evaluated. RESULTS: The mean lung density increased and LAA% decreased in all patients at expiratory phase compared with inspiratory phase. The inspiratory density indices and expiratory mean lung density correlated only with FEV(1)/forced vital capacity (FVC). Expiratory LAA% correlated more strongly than other variables with FEV(1)/FVC and with indices of peripheral airflow obstruction. Expiratory/inspiratory ratios of LAA% and mean lung density correlated, the former more strongly, with disease severity, residual volume/total lung capacity, and airway sensitivity, as well as with indices of global (FEV(1) and FEV(1)/FVC) and peripheral airflow obstruction. CONCLUSION: Expiratory/inspiratory high-resolution computed tomography is useful for assessing small airways disease in asthma. Small airways involvement is associated with airflow obstruction, airway hypersensitivity, and more severe disease. CLINICAL IMPLICATIONS: Small airways are an important therapeutic target in asthma.     

Lung volumes and diffusion capacity in sickle cell trait

Patients with sickle cell anemia have a restrictive ventilatory pattern, with reduction in diffusion capacity of the lung (DLco) and lung volumes. Diffusion capacity and lung volumes are reported as either normal or reduced in subjects with sickle cell trait. Thirteen subjects with sickle cell trait, age range 25 to 79 years, were compared with 13 normal subjects matched for age, sex, height, and smoking patterns. There was no significant difference in mean values of DLco or lung volume for the two groups. Neither was there a consistent difference for age-matched individuals. Normal lung function in sickle cell trait as opposed to sickle cell disease is probably related to the fact that the former have fewer, if any, pulmonary infectious and infarctive episodes.     

犬慢性肺缺血再灌注损伤的病理形态学观察

目的 研究犬慢性缺血再灌注肺损伤的病理形态学改变。方法 利用4只杂种犬建立慢性肺缺血再灌注实验模型，在光镜和电镜下观察慢性缺血期和再灌注期肺组织病理形态学改变，计算受损肺泡百分率。结果 缺血期：左肺部分区域灶性肺泡出血及肺泡膨胀不全，部分肺泡上皮细胞及肺血管内皮细胞线粒体空泡化、嵴溶解，同例对照右肺正常；再灌注期：左肺肺泡出血加重，肺间质和肺泡腔内有水肿液，肺血管内中性粒细胞聚集，受损肺泡百分率明显增加，部分肺泡上皮细胞和肺血管内皮细胞线粒体空泡化、嵴溶解加重，并出现肺泡上皮细胞坏死，同例右肺较左侧病变轻。结论 肺组织缺血期损伤不明显，再灌注期出现比较明显的肺损伤。     

定量CT在评估类风湿性关节炎相关间质性肺病中的应用

目的:探究胸部CT定量分析对于类风湿性关节炎相关间质性肺病（RA-ILD）患者肺间质改变早期诊断及病情评估的价值。方法:收集临床确诊RA患者105例,同时收集胸部CT无间质改变的非结缔组织病患者对照组80例。测量两组研究对象肺总体积（TLV）,利用定量CT肺部密度直方图计算CT值为-200~-700 HU的肺体积占全肺体积百分比（LAA-200~-700%）、CT值小于-950 HU的肺体积占全肺体积百分比（LAA-950%）、主动脉直径（AD）、肺动脉干直径（PAD）、主肺动脉干比值（AD/PAD）、左肺下叶直径2 mm支气管周围血管数量及面积（视区范围80 mm2）。比较RA患者组与对照组的测量值差异。结果:RA患者组与对照组相比,TLV、LAA-200~-700%、PAD、左肺下叶直径为2 mm的支气管视区范围为80 mm2时肺血管数量及面积均存在差异,其中RA患者组TLV为（4 047.60±1 160.11） mL,小于对照组（4 507.30±1 207.50） mL;LAA-200~-700%为14.42%±8.62%,大于对照组10.40%±3.87%,PAD为（26.39±3.59） mm,大于对照组（25.27±2.57） mm;RA组左肺下叶直径为2 mm支气管层面视区范围为80 mm2时肺血管数量为13.3±6.28,面积为（105.48±59.07） mm2;对照组血管数量为17.06±4.70,血管面积为（164.88±46.02） mm2,差异有统计学意义（P<0.001）。结论:RA-ILD患者肺部与对照组相比有差异,定量CT能有效识别评估RA-ILD早期肺血管改变。     

Non-invasive diagnosis of early pulmonary disease in PECAM-deficient mice using infrared pulse oximetry

Pulse oximetry is a common tool for detecting reduced pulmonary function in human interstitial lung diseases. It has not previously been used in a mouse model of interstitial lung disease. Further, platelet endothelial cell adhesion molecule deficient mice rarely show symptoms until disease is advanced.Using blood oxygen saturation, different stages of disease could be identified in a non-invasive manner. These stages could be correlated to pathology. Collagen deposition, using Picrosirius Red, did correlate with blood oxygen saturation. These studies are the first to show the use of an infrared pulse oximetry system to analyze the progression of a fibrotic interstitial lung disease in a mouse model of the human diseases. Further, these studies show that an early alveolar damage/enlargement event precedes the fibrosis in this mouse model, a stage that represents the best targets for disease analysis and prevention. This stage does not have extensive collagen deposition. Most importantly, targeting this earliest stage of disease for therapeutic intervention may lead to novel treatment for human disease.     

MRP14 is elevated in the bronchoalveolar lavage fluid of fibrosing interstitial lung diseases

Pulmonary fibrosis is defined by an overgrowth of fibroblasts and extracellular matrix deposition, and results in respiratory dysfunction that is often fatal. It is the end stage in many chronic inflammatory interstitial lung diseases (ILD) such as sarcoidosis and idiopathic pulmonary fibrosis (IPF). The myeloid‐related proteins (MRPs) belong to the S100 family of calcium‐binding proteins and are highly expressed by neutrophils, macrophages and epithelial cells during chronic inflammation. MRP14 stimulates fibroblast proliferation in vitro and is expressed in granulomas from sarcoidosis patients. We hypothesized that MRP14 may be a biomarker for fibrotic interstitial lung diseases. The objective of this study was to investigate whether levels of MRP14 in the bronchoalveolar lavage fluid (BALF) of patients with sarcoidosis and IPF correlate with clinical parameters. We used an enzyme‐linked immunosorbent assay (ELISA) to measure MRP14 in BALF of 74 sarcoidosis patients, 54 IPF patients and 19 controls. Mean BALF levels of MRP14 were elevated significantly in IPF (P < 0·001) and sarcoidosis (P < 0·05) patients compared to controls. MRP14 levels were associated linearly with sarcoidosis disease severity based on chest radiographic stage. Moreover, BALF MRP14 levels were correlated inversely with diffusion capacity and forced vital capacity in sarcoidosis patients. In IPF patients, a correlation with BALF neutrophil percentage was found. In conclusion, BALF MRP14 levels are elevated in IPF and sarcoidosis and are associated with disease severity in sarcoidosis. The results support the need for further studies into the role of MRP14 in the pathogenesis of lung fibrosis.     

Gremlin localization and expression levels partially differentiate idiopathic interstitial pneumonia severity and subtype

Idiopathic pulmonary fibrosis (IPF) (histopathology of usual interstitial pneumonia, UIP) and non-specific interstitial pneumonia (NSIP) are diseases characterized by loss of normal lung architecture and function. The differential diagnosis between IPF/UIP and NSIP may be difficult. The levels of bone morphogenetic protein (BMP)-4 antagonist gremlin are up-regulated in IPF/UIP. The present study was performed to clarify whether the localization or the mRNA expression of gremlin or BMP-4 could be used in the differential diagnosis or assessment of severity of IPF/UIP and NSIP. Gremlin and BMP-4 immunoreactivities were quantitated from 24 UIP and 12 NSIP lung specimens. Quantitative real-time polymerase chain reaction analyses were performed to compare gremlin and BMP-4 expression between UIP (n = 8) and NSIP (n = 5) biopsies. Immunohistochemical positivity and mRNA levels were correlated to lung function parameters. In IPF/UIP biopsies, gremlin was detected mainly in the thickened lung parenchyma, whereas in NSIP it was observed in the alveolar epithelium. BMP-4-positive (BMP-4+) cells were detected solely in the alveolar wall. The percentage of gremlin-positive area was higher in IPF/UIP (5.1 +/- 0.6) than in NSIP (1.8 +/- 0.7) (n = 36, p < 0.0001). Gremlin mRNA levels were higher in advanced UIP (p = 0.008) and NSIP (p = 0.007) biopsies than in the normal control lung. A negative correlation was found between the specific diffusion capacity corrected for alveolar volume (DLCO/VA) and gremlin mRNA levels (r = - 0.69, p = 0.007). The highest numbers of BMP-4+ cells were found in NSIP biopsies. BMP-4 mRNA levels correlated positively with forced vital capacity (r = 0.801, p < 0.0001) and diffusion capacity. Parenchymal gremlin immunoreactivity is thus suggestive of a UIP-type interstitial pneumonia. Gremlin expression levels correlating negatively and BMP-4 levels positively with disease severity support recent observations of a fibroprotective role for the BMPs.     

Scintigraphic evidence for relief of airways obstruction in cystic fibrosis

A simple scheme for quantifying lung perfusion scintigrams was developed to evaluate the efficacy of a therapeutic regimen for the relief of airways obstruction in cystic fibrosis patients. Ten hospitalized patients were given conventional therapy including administration of intravenous antibiotics, mucolytic aerosols, chest physical therapy, and adequate nutrition and hydration as adjuncts to a single bronchoscopic bronchial washing procedure. Quantitative scoring of the lung scintigram was based upon the severity of the perfusion defects in equivalent upper and lower lung fields, as viewed from right and left posterior oblique projections. Seven to ten days following bronchoscopic washing, scintigraphic scores were found to correlate with changes in both the forced vital capacity and the one-second, time forced expiratory volume (r = 0.78, 0.70, respectively; P <.05). The severity of defective lung perfusion indicated the loss of lung volume and perfusion due to airways obstruction and secondary hypoxic vasoconstriction. Chest radiography was less reflective of improvement than lung scintigraphy. It was concluded that serial pulmonary perfusion scintigrams provide a sensitive tool for evaluating the relief of airways obstruction in cystic fibrosis.     

Anchoring fibrils. A new connective tissue structure in fibrotic lung disease

Electron microscopic studies of lung were made and compared in 17 patients with lung disease (10 with idiopathic pulmonary fibrosis, 3 with collagen--vascular diseases, 3 with sarcoidosis, and 1 with chronic eosinophilic pneumonia) and in 5 control patients. In control patients, the alveolar epithelial cells were normal, and no hemidesmosomes were present between the plasma membranes and the basal laminae. In comparison, cuboidal alveolar epithelial cells were present in 15 of the patients with fibrotic lung disease; in 9 of these the alveolar epithelial cells were multilayered. In 7 of the latter 9 patients (5 with idiopathic pulmonary fibrosis and 2 with collagen-vascular diseases), the basal laminae of the alveolar epithelial cells were attached to the plasma membranes by hemidesmosomes and to the underlying interstitial connective tissue by "anchoring fibrils." These fibrils measured from 4000 to 6000 A in length and from 200 to 600 A in width. One or both ends of the anchoring fibrils inserted into thebasal lamina, often forming arcs through which collagen fibrils and connective tissue microfibrils penetrated. Anchoring fibrils showed a complex pattern of transverse banding, which differed from that of collagen and appeared to be symmetric about the center of the fibril. These anchoring fibrils, which resemble those in normal skin and other tissues, were not found in lungs of control patients. In addition, there was a significant correlation between the severity of the pulmonary fibrosis and the presence of anchoring fibrils. These observations suggest that in severe fibrotic lung disease, anchoring fibrils reinforce the attachment of the basal lamina of multilayered alveolar epithelial cells to interstitial connective tissue.     

Bronchiolitis interstitial pneumonitis: a pathologic study of 31 lung biopsies with features intermediate between bronchiolitis obliterans organizing pneumonia and usual interstitial pneumonitis, with clinical correlation

Bronchiolitis combined with interstitial pneumonitis generally has been equated with bronchiolitis obliterans organizing pneumonia (BOOP). We describe our experience with lung biopsies that had both bronchiolar and interstitial diseases. We studied 31 patients who had respiratory difficulty leading to open lung biopsy, which showed a combination of both prominent bronchiolitis and prominent interstitial pneumonitis. We compared these cases clinically and pathologically with 6 other pulmonary diseases, namely, bronchiolitis obliterans, BOOP, nonspecific interstitial pneumonitis, usual interstitial pneumonitis, airway-centered interstitial fibrosis, and idiopathic bronchiolocentric interstitial pneumonia, and with 10 cases of cystic fibrosis, an unrelated disease with both bronchiolar and interstitial pathology. The commonality of our cases was a combination of bronchiolitis and interstitial inflammation and fibrosis but little or no intra-alveolar organizing pneumonia. Bronchiolitis obliterans with organizing pneumonia involved less area than the interstitial pneumonitis in each case. All 19 patients for whom we had follow-up received corticosteroids for their pulmonary diseases. Seven patients had improvement in symptoms and pulmonary function test results and radiographic findings, 5 patients experienced subjective improvement with unchanged results of pulmonary function tests or chest x-ray, 1 patient's condition was unchanged, 6 patients' disease worsened, and 4 of these 6 died. The natural history of these cases, which we have designated bronchiolitis interstitial pneumonitis, seems more sanguine than usual interstitial pneumonitis and worse than BOOP at least in the short term. On the one hand, response to corticosteroids was not as frequent as generally accepted for BOOP. On the other hand, disease did not progress in most patients on corticosteroids.     

Lung diseases after bone marrow transplantation

Summary The case histories of 72 subsequently treated patients — 44 with acute leukemia, 10 with chronic myeloid leukemia, 16 with severe aplastic anemia and 2 with neuroblastoma — were analyzed after bone marrow transplantation (BMT) with respect to pulmonary diseases. Thirty-eight patients suffered from a total of 51 pulmonary complications, which led to death in 20. Of 13 patients, 3 died of bacterial pneumonia, all of them during granulocytopenia; 2 of 6 patients died of fungal pneumonia and 2 out of 3 of a mixed bacterialmycotic infection. Adult respiratory distress syndrome (ARDS) led to death in 2 patients. A granulocyte count under 500/µl correlated significantly (P<0.002) with the fatal outcome of bacterial, fungal and ARDS pneumonia as well as with bronchitis. Viral pneumonia led to death in 8 of 9 patients; in each there was a significant correlation (P<0.05) with graft-versus-host disease (GvHD). Patients with repeated episodes of pulmonary illness had significantly more chronic GvHD (P<0.05); several of these patients displayed a reduction in helper T cells and an increase in suppressor T cells in the peripheral blood. The natural killer (NK) cells were reduced and the percentage of activated NK cell level lay between 6% and 69%. B-cells were absent or deficient. These findings explain in part the absence of specific antibody reactivity. Five of these patients also contracted GvHD-associated obstructive bronchiolitis, which did not respond to therapy. Pulmonary infiltrates of unknown origin (including idiopathic interstitial pneumonia) occurred in 8 of the patients (11.1%), with a fatal outcome in 3 patients. Significant changes (P<0.05) in lung function after BMT appeared in the form of reduced vital capacity (VC) increased residual volume (RV) and an increase in RV expressed as the percentage of total lung capacity. Pulmonary diseases were the most common complication and cause of death in our patients after BMT.Abbreviations AEL acute erythroid leukemia - AHTCG anti-human T-cell globulin - ALL acute lymphoblastic leukemia - AML acute myeloid leukemia - ARDS adult respiratory distress syndrome - AUL acute undifferentiated leukemia - BMT bone marrow transplantation - CR complete remission - CML chronic myeloid leukemia - CMV cytomegalovirus - Ext. extensive - GvHD graft versus host disease - Lim. limited - PR partial remission - Rel. relapse - SAA severe aplastic anemia - VZV varicella zoster virus.Lung function tests - DLCO single-breath CO-diffusion capacity - FEV₁ forced expiratory volume in 1 s - KCO Krogh's constant - MBC maximal breathing capacity - RAW airway resistance - RV residual volume - SRAW specific airway resistance - TGV thoracic gas volume - TLC total lung capacity - VC vital capacity Supported in part by SFB 120, A2, B1, C1, F2     

Circulating progenitor cells are reduced in patients with severe lung disease

Patients with chronic severe lung disease are prone to develop pulmonary vascular remodeling, possibly through pulmonary endothelial dysfunction. Circulating endothelial progenitor cells (EPCs) are involved in maintenance of endothelial homeostasis. The aim of this study was to assess whether obstructive and restrictive lung diseases are associated with modification of EPC number in peripheral blood. The study was cross-sectional and involved patients with obstructive (n = 15) and restrictive (n = 15) lung disease on oxygen therapy and 15 control subjects. Circulating EPCs were defined by the surface expression of CD34, CD133, and kinase-insert domain receptor. Results from spirometric tests, blood gas analyses, and blood cell counts have been related to EPC numbers. Patients with chronic hypoxia and severe lung disease showed lower levels of all progenitors than do control subjects. A consensual further reduction of EPC was found in restrictive patients in comparison with obstructive patients. Among restrictive patients, EPC reduction was related to reduced lung volumes and impaired alveolo-arterial diffusion, whereas progenitor cell levels were directly related to erythrocyte number. Considering obstructive patients, significant correlations were found between progenitor cell levels and bronchial obstruction and between progenitor cell levels and arterial oxygen tension. These findings demonstrate a reduction of EPCs in patients with chronic lung disease and long-lasting hypoxia. This alteration was more evident in restrictive patients and correlated to disease severity. Depletion of circulating EPCs may be involved in altered endothelial homeostasis of pulmonary circulation in these disorders.     

肺淋巴管功能及其在肺部疾病的研究进展

淋巴管系统是一个单向网络,淋巴液沿着一系列的淋巴管道向心流动,最终汇入静脉,因此淋巴系统也可以认为是静脉系统的辅助部分,是心血管系统的重要组成部分。淋巴管系统负责调节组织液的平衡、脂质吸收及免疫监测等功能,其失调会导致多种疾病。肺淋巴管系统在多种肺部疾病中扮演着非常重要的角色,涉及维持体液平衡,抗原呈递等,此外还会影响到肺移植后移植体的存活等。本文针对肺淋巴管以及其在肺部疾病中的作用进行介绍。     

Lung mast cell density defines a subpopulation of patients with idiopathic pulmonary fibrosis

Cha S‐I, Chang C S, Kim E K, Lee J W, Matthay M A, Golden J A, Elicker B M, Jones K, Collard H R & Wolters P J (2012) Histopathology  61, 98–106 Lung mast cell density defines a subpopulation of patients with idiopathic pulmonary fibrosis Aims: The relationship of mast cells to the pathogenesis of lung fibrosis remains undefined despite recognition of their presence in the lungs of patients with pulmonary fibrosis. This study was performed to characterize the relationship of mast cells to fibrotic lung diseases. Methods and results: Lung tissues from patients with idiopathic pulmonary fibrosis (IPF), chronic hypersensitivity pneumonitis (HP), systemic sclerosis (SSc)‐related interstitial lung disease (ILD) and normal individuals were subjected to chymase immunostaining and the mast cell density quantified. Eosinophils were quantified by immunostaining for eosinophil peroxidase. Changes in lung function were correlated with mast cell density. Lung tissue obtained from IPF patients had a higher density of chymase‐immunoreactive mast cells than that from patients with HP, SSc‐related ILD or normal lungs. IPF lung tissue had a higher density of eosinophils than normal lung. There was no correlation between mast cell density and eosinophil density in IPF lung. IPF patients with high mast cell density had a slower rate of decline in forced vital capacity (FVC) than IPF patients with low mast cell density. Conclusions: Mast cell density in IPF lungs is higher than in other fibrotic lung diseases and normal lungs. Increased mast cell density in IPF may predict slower disease progression.     

Pulmonary involvement in type 1 Gaucher disease: functional and exercise findings in patients with and without clinical interstitial lung disease

Pulmonary disease is a well-known complication of Type 1 Gaucher disease (GD), although its incidence is not well established and its severity varies. The purpose of this study was to determine the frequency and extent of pulmonary involvement in patients with GD. Pulmonary involvement was assessed by history, physical examination and chest radiograph in 150 consecutive patients with Type 1 GD presenting at a specialized center for genetic diseases. Five patients were noted to have clinical evidence of pulmonary involvement. Full pulmonary function tests were performed in these five patients and in an additional 13 patients randomly selected from the remaining 145. Many of the 18 patients also underwent radionuclide body imaging with 67 Gallium citrate and 111Indium-tagged leucocyte scans, as well as incremental cardiorespiratory exercise tests. Lung biopsies were available in two patients with lung disease, and a second examination of lung tissue was performed in one of these two patients post-mortem. Clinical lung disease was detected in five patients. All five had dyspnea, diffuse infiltrates, restrictive impairment and low single breath CO diffusing capacity (DLCOSB). Two of these patients underwent exercise testing and showed abnormalities consistent with lung disease (ventilatory limitation, excessive ventilation and increased dead space) as well as decreased VO2 max. and anaerobic threshold (AT). In contrast, in the other 13 patients, physical examination, chest radiographs and pulmonary function were normal (except for a low DLCOSB in one patient). Responses on exercise testing (performed in six of the 13 patients) were consistent with a circulatory impairment (decreased VO2 max. and AT). Our study found that <5% of patients with Type 1 GD have clinical interstitial lung disease. In addition, we found that some patients, without evident lung involvement, may experience limitations in physical exertion and are easily fatigued; this is attributable to impaired circulation.     

Effect of diet-ingested pirfenidone on pulmonary function, cardiovasculature and blood gas measurements in rats.

Pirfenidone is an antifibrotic drug that we have shown attenuates the increase in collagen buildup in hamsters exposed to bleomycin, in turn reducing pulmonary function and blood gas decrements seen in this model of interstitial pulmonary fibrosis. The systemic effects of pirfenidone ingestion, however, are unknown. We examined the effect of diet-ingested pirfenidone on pulmonary function, systemic and pulmonary cardiovasculature and blood gas measurements, breathing pattern and lung hydroxyproline content in rats fed either a control diet or a diet containing 0.5% pirfenidone. Residual volume was higher and expiratory reserve volume lower in the pirfenidone group, with no change in functional residual capacity. Tidal volume was also lower in the pirfenidone group, with no change in the overall level of ventilation. There was a trend toward a reduced hydroxyproline content and an increased lung compliance in the pirfenidone group. There were no differences in systemic or pulmonary pressures, cardiac output, stroke volume, heart rate, pH or blood gases between the two groups. These data indicate that pirfenidone has few systemic side-effects but may have a mild effect on the basal level of lung collagen content with resulting clinical changes in some pulmonary function measurements and changes in breathing pattern.