Masanori Akira

Interobserver Variability in the CT Assessment of Honeycombing in the Lungs

PURPOSE To quantify observer agreement and analyze causes of disagreement in identifying honeycombing at chest computed tomography (CT). MATERIALS AND METHODS The institutional review board approved this multiinstitutional HIPAA-compliant retrospective study, and informed patient consent was not required. Five core study members scored 80 CT images with a five-point scale (5 = definitely yes to 1 = definitely no) to establish a reference standard for the identification of honeycombing. Forty-three observers from various subspecialties and geographic regions scored the CT images by using the same scoring system. Weighted κ values of honeycombing scores compared with the reference standard were analyzed to investigate intergroup differences. Images were divided into four groups to allow analysis of imaging features of cases in which there was disagreement: agreement on the presence of honeycombing, agreement on the absence of honeycombing, disagreement on the presence of honeycombing, and other (none of the preceding three groups applied). RESULTS Agreement of scores of honeycombing presence by 43 observers with the reference standard was moderate (Cohen weighted κ values: 0.40-0.58). There were no significant differences in κ values among groups defined by either subspecialty or geographic region (Tukey-Kramer test, P = .38 to >.99). In 29% of cases, there was disagreement on identification of honeycombing. These cases included honeycombing mixed with traction bronchiectasis, large cysts, and superimposed pulmonary emphysema. CONCLUSION Identification of honeycombing at CT is subjective, and disagreement is largely caused by conditions that mimic honeycombing.

Inhaled granulocyte/macrophage-colony stimulating factor as therapy for pulmonary alveolar proteinosis.

RATIONALE Inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) is a promising therapy for pulmonary alveolar proteinosis (PAP) but has not been adequately studied. OBJECTIVES To evaluate safety and efficacy of inhaled GM-CSF in patients with unremitting or progressive PAP. METHODS We conducted a national, multicenter, self-controlled, phase II trial at nine pulmonary centers throughout Japan. Patients who had lung biopsy or cytology findings diagnostic of PAP, an elevated serum GM-CSF antibody level, and a Pa(O(2)) of less than 75 mm Hg entered a 12-week observation period. Those who improved (i.e., alveolar-arterial oxygen difference [A-aDO(2)] decreased by 10 mm Hg) during observation were excluded. The rest entered sequential periods of high-dose therapy (250 microg Days 1-8, none Days 9-14; x six cycles; 12 wk); low-dose therapy (125 microg Days 1-4, none Days 5-14; x six cycles; 12 wk), and follow-up (52 wk). MEASUREMENTS AND MAIN RESULTS Fifty patients with PAP were enrolled in the study. During observation, nine improved and two withdrew; all of these were excluded. Of 35 patients completing the high- and low-dose therapy, 24 improved, resulting in an overall response rate of 62% (24/39; intention-to-treat analysis) and reduction in A-aDO(2) of 12.3 mm Hg (95% confidence interval, 8.4-16.2; n = 35, P < 0.001). No serious adverse events occurred, and serum GM-CSF autoantibody levels were unchanged. A treatment-emergent correlation occurred between A-aDO(2) and diffusing capacity of the lung, and high-resolution CT revealed improvement of ground-glass opacity. Twenty-nine of 35 patients remained stable without further therapy for 1 year. CONCLUSIONS Inhaled GM-CSF therapy is safe, effective, and provides a sustained therapeutic effect in autoimmune PAP. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN18931678), www.jmacct.med.or.jp/english (JMA-IIA00013).

Usual Interstitial Pneumonia and Nonspecific Interstitial Pneumonia with and without Concurrent Emphysema: Thin-Section CT Findings

PURPOSE To determine whether concurrent emphysema influences the distinction between usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP) at thin-section computed tomography (CT). MATERIALS AND METHODS Institutional review board approval was obtained for this retrospective study; informed consent was not required. The study included 54 patients with NSIP and 42 patients with UIP (55 men, 41 women; mean age, 60.2 years +/- 9.2 [standard deviation]; age range, 33-77 years). Two independent readers assessed the CT images and made a first-choice diagnosis. The appearances of UIP and NSIP at CT were compared with univariate and multivariate analyses. Receiver operating characteristic curves were used to determine how concurrent emphysema influences the distinction of UIP from NSIP at thin-section CT. RESULTS The diagnosis was correct in 136 (71%) of 192 readings. In patients with concurrent emphysema, the diagnosis was correct in 30 (44%) of 68 readings. Sensitivity, specificity, and accuracy for diagnosis were lower in patients with concurrent emphysema than in patients without concurrent emphysema. In patients with concurrent emphysema, there were no significant differences in extent of fibrosis, extent of honeycombing, extent of consolidation, coarseness of fibrosis score, extent of traction bronchiectasis, upper lung irregular lines, peribronchovascular distribution, and nodules between UIP and NSIP. According to multivariate analysis, the CT feature that helped best differentiate UIP from NSIP in patients with emphysema was traction bronchiolectasis. CONCLUSION Concurrent emphysema influenced the distinction between UIP and NSIP.

Acute respiratory distress syndrome and acute interstitial pneumonia : Comparison of thin-section CT findings

Purpose The purpose of this work was to compare the thin-section CT findings of acute respiratory distress syndrome (ARDS) with those of acute interstitial pneumonia (AIP). Method The thin-section CT scans from 25 patients with ARDS and 25 with AIP were independently assessed by two observers without knowledge of clinical and pathologic data. The presence, extent, and distribution of various CT findings were independently analyzed. Results Honeycombing was seen more frequently in lobes of patients with AIP (26%) than in lobes with ARDS (8%) (p < 0.001). Compared with patients with ARDS, a greater number of patients with AIP had a predominantly lower lung zone distribution (p < 0.05) and a symmetric distribution (p < 0.05) of the parenchymal abnormalities. Conclusion Patients with AIP have a greater prevalence of honeycombing and are more likely to have a symmetric bilateral distribution and a lower lung zone predominance than patients with ARDS. However, significant overlap exists among the CT findings.

Drug-Induced Eosinophilic Pneumonia: High-Resolution CT Findings in 14 Patients

OBJECTIVE The purpose of this study was to evaluate the high-resolution CT findings of drug-induced eosinophilic pneumonias. CONCLUSION Drug-induced eosinophilic pneumonias usually manifest as areas of consolidation and ground-glass opacity most commonly involving the outer third of the lungs.

Predictors of the clinical effects of pirfenidone on idiopathic pulmonary fibrosis

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with a poor prognosis. Recently, pirfenidone was reported to slow the rate of decline in vital capacity and improve progression-free survival in IPF. The purpose of this study was to clarify the factors that predicted a good response to pirfenidone, as well as its adverse effects. METHODS Forty-one IPF cases, treated with pirfenidone from January 2009 to January 2011, were enrolled in this investigation. Disease severity was classified into grades I-IV, as defined by the Japanese Respiratory Society (JRS). Short-term responsiveness to pirfenidone was evaluated by the modified criteria of the JRS. Predictors of nausea, anorexia, or both that represented important adverse effects were examined by multivariate Cox proportional hazard analyses. Predictors of short-time responsiveness were examined by multivariate logistic regression analyses. RESULTS Diagnosed by a surgical lung biopsy (SLB), the mild cases of grade I/II were predictors of good, short-term responsiveness. Patients taking acid-secretion inhibitors, including proton pump inhibitors and histamine H2-receptor antagonists, showed less anorexia, nausea, or both. Only 1 case was administered drugs to activate gastrointestinal motility. CONCLUSIONS We concluded that IPF patients with a mild disease, diagnosis by SLB, or both showed indications of a good response to pirfenidone. In addition, acid-secretion inhibitors may reduce the frequency of anorexia, nausea, or both from pirfenidone.

Duration of Benefit in Patients With Autoimmune Pulmonary Alveolar Proteinosis After Inhaled Granulocyte-Macrophage Colony-Stimulating Factor Therapy

BACKGROUND Treatment of autoimmune pulmonary alveolar proteinosis (aPAP) by subcutaneous injection or inhaled therapy of granulocyte-macrophage colony-stimulating factor (GM-CSF) has been demonstrated to be safe and efficacious in several reports. However, some reports of subcutaneous injection described transient benefit in most instances. The durability of response to inhaled GM-CSF therapy is not well characterized. METHODS To elucidate the risk factors for recurrence of aPAP after GM-CSF inhalation, 35 patients were followed up, monitoring for the use of any additional PAP therapies and disease severity score every 6 months. Physiologic, serologic, and radiologic features of the patients were analyzed for the findings of 30-month observation after the end of inhalation therapy. RESULTS During the observation, 23 patients remained free from additional treatments, and twelve patients required additional treatments. There were no significant differences in age, sex, symptoms, oxygenation indexes, or anti-GM-CSF antibody levels at the beginning of treatment between the two groups. Baseline vital capacity (% predicted, %VC) were higher among those who required additional treatment (P<.01). Those patients not requiring additional treatment maintained the improved disease severity score initially achieved. A significant difference in the time to additional treatment between the high %VC group (%VC≥80.5) and the low %VC group was seen by a Kaplan-Meier analysis and a log-rank test (P<.0005). CONCLUSIONS These results demonstrate that inhaled GM-CSF therapy sustained remission of aPAP in more than one-half of cases, and baseline %VC might be a prognostic factor for disease recurrence. TRIAL REGISTRY ISRCTN Register and JMACCT Clinical Trial Registry; No.: ISRCTN18931678 and JMAIIA00013; URL: http://www.isrctn.org and http://www.jmacct.med.or.jp.

Long-term follow-up high-resolution CT findings in non-specific interstitial pneumonia

Background The aims of this study were to retrospectively assess the change in findings on follow-up CT scans of patients with non-specific interstitial pneumonia (NSIP; median, 72 months; range, 3–216 months) and to clarify the correlation between the baseline CT findings and mortality. Methods The study included 50 patients with a histologic diagnosis of NSIP. Two observers evaluated the high-resolution CT (HRCT) findings independently and classified each case into one of the following three categories: (1) compatible with NSIP, (2) compatible with UIP or (3) suggestive of alternative diagnosis. The correlation between the HRCT findings and mortality was evaluated using the Kaplan–Meier method and the log-rank test, as well as Cox proportional hazards regression models. Results Ground-glass opacity and consolidation decreased, whereas coarseness of fibrosis and traction bronchiectasis increased on the follow-up HRCT scans, however, in 78% of cases the overall extent of parenchymal abnormalities had no change or decreased. Patients with HRCT diagnosed compatible with NSIP had a longer survival than those with HRCT findings more compatible UIP or an alternative diagnosis. On multivariate analysis, the coarseness of fibrosis alone was associated with prognosis (HR: 1.480; 95% CIs 1.100 to 1.990). Conclusions The HRCT patterns seen in patients with a histopathologic diagnosis of NSIP progress in a variable manner. Overall disease extent may decrease over time in some, while fibrosis may progress in others. The initial HRCT diagnosis may impact survival in this group of patients.

Pleuroparenchymal fibroelastosis from a consecutive database: a rare disease entity?

Pleuroparenchymal fibroelastosis (PPFE) is a rare condition characterised by predominantly upper lobe involvement with pleural fibrosis and subjacent parenchymal fibroelastosis [1, 2]. Idiopathic PPFE (IPPFE), which was included in the rare idiopathic interstitial pneumonias (IIPs) in the update of the international multidisciplinary classification of IIPs published in 2013 [3], was first described in the Japanese literature by Amitani et al. in 1992 [4]. PPFE has been reported to be associated with drugs, chronic hypersensitivity pneumonia, collagen vascular diseases, infections, and bone marrow transplantations [5–8]. However, the frequency of PPFE occurrence has been uncertain. We hypothesised that PPFE was not a rare disease entity and conducted this study. Informed consent was obtained from all patients, and the Institutional Review Board of the National Hospital Organization Kinki-Chuo Chest Medical Center (KCCMC) (Sakai City, Japan) approved this study. Idiopathic pleuroparenchymal fibroelastosis is an acceptable entity among IIPs and not as rare as previously reported http://ow.ly/I5NEz

Accuracy of chest high-resolution computed tomography in diagnosing diffuse cystic lung diseases

The diffuse cystic lung diseases (DCLDs) are a group of pathophysiologically heterogeneous processes characterised by the presence of multiple, thin-walled, air-filled spaces within the pulmonary parenchyma [1]. The differential diagnosis of DCLDs includes lymphangioleiomyomatosis (LAM), follicular bronchiolitis (FB), lymphocytic interstitial pneumonia (LIP), Birt–Hogg–Dubé syndrome (BHD), pulmonary Langerhans cell histiocytosis (PLCH), amyloidosis, light chain deposition disease, cystic metastases, infectious entities such as Pneumocystis, and other aetiologies [2]. Bronchiectasis and bullous changes seen in chronic obstructive pulmonary disease can also produce high-resolution computed tomography (HRCT) patterns that mimic the DCLDs. Correct diagnosis of diffuse cystic lung diseases is established in most cases by critical review of HRCT features http://ow.ly/NvrCc