Idiopathic pulmonary fibrosis (IPF) is a fatal disorder without an effective therapy to date. In a double-blind, randomized, placebo-controlled trial, 107 patients were prospectively evaluated for efficacy of a novel compound, pirfenidone. The difference in the change in the lowest oxygen saturation by pulse oximetry (SpO2) during a 6-minute exercise test, the primary endpoint, from baseline to 6 months was not significant between the two groups (p = 0.0722). In a prespecified subset of patients who maintained a SpO2 greater than 80% during a 6-minute exercise test at baseline, the lowest SpO2 improved during a 6-minute exercise test in the pirfenidone group at 6 and 9 months (p = 0.0069 and 0.0305, respectively). Positive treatment effect was demonstrated in secondary endpoints: (1) change in VC measurements at 9 months (p = 0.0366) and (2) episodes of acute exacerbation of IPF occurring exclusively in the placebo group during the 9 months (p = 0.0031). Significant adverse events were associated with pirfenidone; however, adherence to treatment regimen was similar between pirfenidone and placebo groups. In conclusion, treatment with pirfenidone improved VC and prevented acute exacerbation of IPF during the 9 months of follow-up. Future long-term studies are needed to clarify the overall safety and efficacy of pirfenidone in IPF.

Chronic obstructive pulmonary disease (COPD) is characterized by the presence of airflow obstruction caused by emphysema or airway narrowing, or both. Low attenuation areas (LAA) on computed tomography (CT) have been shown to represent macroscopic or microscopic emphysema, or both. However CT has not been used to quantify the airway abnormalities in smokers with or without airflow obstruction. In this study, we used CT to evaluate both emphysema and airway wall thickening in 114 smokers. The CT measurements revealed that a decreased FEV(1) (%predicted) is associated with an increase of airway wall area and an increase of emphysema. Although both airway wall thickening and emphysema (LAA) correlated with measurements of lung function, stepwise multiple regression analysis showed that the combination of airway and emphysema measurements improved the estimate of pulmonary function test abnormalities. We conclude that both CT measurements of airway dimensions and emphysema are useful and complementary in the evaluation of the lung of smokers.

Based on past difficulties in clinically differentiating patients with idiopathic pulmonary fibrosis (IPF), bronchiolitis obliterans-organizing pneumonia (BOOP), and nonspecific interstitial pneumonia/fibrosis (NSIP), which all manifest clinically as interstitial lung disease, experience with pathologically confirmed examples of the three diseases was reviewed to compare clinical profiles and prognosis and to define NSIP more clearly. Thirty-one patients (15 males and 16 females) were pathologically identified as NSIP and subclassified into either the cellular (n=16) or fibrotic group (n=15). All 31 patients were clinically considered to be idiopathic NSIP cases. Patients with idiopathic BOOP (n=16) and IPF (n=64) were compared with the NSIP patients. Subacute presentation of interstitial lung disease characterized both idiopathic NSIP and idiopathic BOOP. NSIP patients showed volume loss on a chest radiograph (29.0%) and honeycombing on a computed tomography scan (25.8%); these features were not found in BOOP patients. Bronchoalveolar lavage lymphocytosis was characteristic of both BOOP and NSIP. Two subgroups of NSIP can be recognized histologically: patients in the fibrotic group had a less favourable outcome than those in the cellular group. BOOP and NSIP had a more favourable outcome than IPF. In conclusion, idiopathic nonspecific interstitial pneumonia can be differentiated from other types of idiopathic interstitial pneumonia, both pathologically and clinically.

Increases in the low attenuation areas (LAA) of chest x-ray computed tomography images in patients with chronic obstructive pulmonary disease (COPD) have been reported to ref lect the development of pathological emphysema. We examined the statistical properties of LAA clusters in COPD patients and in healthy subjects. In COPD patients, the percentage of the lung field occupied by LAAs (LAA%) ranged from 2.6 to 67.6. In contrast, LAA% was always <30% in healthy subjects. The cumulative size distribution of the LAA clusters followed a power law characterized by an exponent D. We show that D is a measure of the complexity of the terminal airspace geometry. The COPD patients with normal LAA% had significantly smaller D values than the healthy subjects, and the D values did not correlate with pulmonary function tests except for the diffusing capacity of the lung. We interpret these results by using a large elastic spring network model and find that the neighboring smaller LAA clusters tend to coalesce and form larger clusters as the weak elastic fibers separating them break under tension. This process leaves LAA% unchanged whereas it decreases the number of small clusters and increases the number of large clusters, which results in a reduction in D similar to that observed in early emphysema patients. These findings suggest that D is a sensitive and powerful parameter for the detection of the terminal airspace enlargement that occurs in early emphysema.High-resolution computed tomography (CT) is a sensitive and noninvasive tool for assessing alterations in lung structure induced by various disease processes. Increases in the low attenuation areas (LAA) in the lung regions of chest x-ray CT images in patients with chronic obstructive pulmonary disease (COPD) have been reported to reflect the development of pathological emphysema (1-4). Nevertheless, previous methods of analyzing lung CT images are limited for general clinical diagnostic purposes (5) because the size and spatial distribution of LAAs are not taken into account. Recently, Uppaluri et al. (6) found that a texture-based adaptive multiple feature method could differentiate between normal and emphysematous tissue with 100% accuracy. However, it is not clear whether this method would detect early emphysema. More recently, Shimizu et al. (7) proposed a promising fractal analysis method for assessing ground-glass opacities in lung CT images. Their approach was able to successfully differentiate between fibrotic and nonfibrotic disease processes.The concept of fractal geometry was developed by Mandelbrot (8) to quantitatively describe the random variations in size and shape seen in natural objects. A fractal object is said to be scale-free because its characteristics are invariant under isotropic scale transformations. Such scale-invariance can be achieved if the object is formed by parts that are similar to the whole. In other words, fractals are self-similar and hence are characterized by power law functions (the only mathematical functions obeying s...

Postmortem studies have shown that airway wall thickening is present in asthmatic patients and may play a pathophysiologic role. We investigated the presence and characteristics of airway wall thickening in patients with asthma, using helical computed tomography. Eighty-one asthmatic patients and 28 healthy control subjects were studied cross-sectionally. Airway wall thickness was assessed by a validated method on the basis of wall area (WA), WA corrected by body surface area (WA/BSA), and WA%, defined as (WA/total area) x 100 at the apical bronchus of the right upper lobe. Airway luminal area (Ai) and Ai/BSA were also examined. Asthma duration and severity, pulmonary function, and serum eosinophil cationic protein levels were evaluated. Intraobserver and interobserver reproducibility of WA, WA%, and Ai measurements were good. As compared with control, WA, WA/BSA, and WA% were significantly increased in patients with mild (n = 13), moderate (39), and severe persistent (22) asthma but not in patients with intermittent asthma (7). Comparison of the four asthmatic subgroups demonstrated thicker airways in more severe disease, but no difference in Ai or Ai/BSA. When all asthmatic patients were analyzed together, WA and WA/BSA correlated with the duration, although weakly, and severity of asthma. WA and WA/BSA negatively correlated with FEV(1) (percentage of predicted), FEV(1)/FVC (%), and FEF(25-75%) (percentage of predicted), whereas WA% negatively correlated with only FEV(1). We conclude that airway wall thickening occurs in patients with asthma and is not limited to those with severe disease. The degree of airway wall thickening may relate to the duration and severity of disease and the degree of airflow obstruction.

aaPulmonary epithelioid haemangioendothelioma (PEH) is a rare tumour of the lung. The disease was originally reported by DAIL and LIEBOW [1] in 1975 as "intravascular bronchoalveolar tumour" (IVBAT), and the majority (65%) patients of the reported 20 patients showed multiple bilateral nodular lesions. In addition, one patient had bronchoalveolar cell carcinoma. The recognition of Weibel-Palade bodies in the cytoplasm of tumour cells of IVBAT by electron microscopy, along with the immunoreactivity of the cytoplasm of tumour cells for factor VIII-related antigen, prompted the realization that IVBAT probably derived from vascular endothelial cells [2][3][4][5][6][7][8][9]. Forty-one patients with soft-tissue neoplasms exhibiting histopathological features similar to IVBAT were reported by WEISS and ENZINGER [10] in 1982. The tumour was termed epithelioid haemangioendothelioma [2,[9][10][11][12], and by 1986 had been reported to occur also in the liver, head and neck area, oral mucosa, bone, mediastinum, diaphragm and brain [13].We reported on two asymptomatic patients with IVBAT (PEH) in the mid-1980s [14,15], and observed partial spontaneous regression of the disease during follow-up in both. In order to evaluate more thoroughly the clinicopathological spectrum of PEH, 21 patients with PEH recruited in Asia (Japan, Korea, Taiwan and Singapore) were studied, who included an additional patient with partial spontaneous regression [16]. The description of all of these patients and their prognostic features form the basis of the present report. Methods Study populationTo obtain data on the clinical and pathological features of PEH in as many patients as possible, a survey was carried out of the Japanese literature of the past 15 yrs and letters were sent to Departments of Medicine, Respiratory Medicine, Radiology and Pathology of 230 major hospitals in Japan. In addition, letters were sent to five major hospitals in Korea, Taiwan, Hong Kong and Singapore. In order to confirm the diagnosis of PEH, the histopathological specimens from 23 patients were reviewed at an International Meeting on PEH held in 1994 in Kyoto, Japan. Six out of the 23 patients have been reviewed previously by one of the present authors (M. Kitaichi) [14][15][16][17].The clinical summary of patients with PEH focused on the features described in the Results section at the time of the first examination by their primary physicians (see Acknowledgements) and at the time of the last clinical contact.The patients were also questioned about the type and duration of therapy, if any. The clinical onset of PEH was defined as the time of onset of pulmonary symptoms attributable to the disease. Clinical improvement or deterioration was assessed by chest radiography. Histopathological and immunohistochemical studiesHistopathological features were analysed according to 18 items [2,9]. The cellularity of tumour cells was graded from Pulmonary epithelioid haemangioendothelioma in 21 patients, including three with partial spontaneous regression. M. Kitaichi, S. Nag...

To evaluate findings of active pulmonary tuberculosis on computed tomographic (CT) scans and their sequential changes before and after antituberculous chemotherapy, 29 patients with newly diagnosed pulmonary tuberculosis and 12 patients with recent reactivation were studied prospectively. The diagnosis of active pulmonary tuberculosis was based on positive acid-fast bacilli in sputum (n = 29) and changes on serial radiographs obtained during treatment (n = 12). Twenty-six patients were followed up with CT during treatment for 1-20 months. Lungs from the cadavers of nine other patients, who died of pulmonary tuberculosis, were studied to provide a pathologic basis for diagnosis. At examination with CT, centrilobular lesions (nodules or branching linear structures 2-4 mm in diameter) were most commonly seen (n = 39 [95%]); in the 26 patients with follow-up, most of these lesions disappeared within 5 months after the start of treatment. In 11 of 12 patients with recent reactivation, CT clearly differentiated old fibrotic lesions from new active lesions. Lesions in and around the small airways appear to be the most characteristic CT feature of early active tuberculosis and may be a reliable criterion for disease activity.

The clinical and pathologic features of 46 patients from Japan, Korea, and Taiwan with pulmonary lymphangioleiomyomatosis (LAM) were studied. Only two (5%) among 40 evaluable treatments were assessed to be effective. Some prognostic factors of LAM were recognized. A reduction of the forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio was a poor prognostic factor at 2 yr after the first examination, with a statistically significant difference (p < 0.05). An increase in the percentage of predicted total lung capacity (%TLC) correlated with a poor prognosis at 2, 3, and 5 yr after the first examination, with statistically significant differences (p < 0.05). Histologically, two types of pulmonary lesions were observed; a predominantly cystic type and a predominantly muscular type. Patients with predominantly cystic LAM lesions showed a tendency to a poor prognosis from 2 to 5 yr after the biopsy. Among open lung biopsy findings, higher grades of abnormal areas were unfavorable as a prognostic factor from 2 to 5 yr after the biopsy, with statistically significant differences (p < 0.05). Higher grades of cystic lesions correlated inversely with survival at 2, 4, and 5 yr after the lung biopsy, with statistically significant differences (p < 0.05).