Rheumatoid lung disease: prognostic analysis of 54 biopsy-proven cases.

OBJECTIVE: To investigate the prognostic significance of histopathological characteristics in patients with biopsy-proven rheumatoid lung disease (RLD). MATERIALS AND METHODS: Retrospective analysis was conducted on samples from 54 RLD patients who underwent surgical lung biopsies (SLBs) at Hamamatsu University Hospital and affiliated hospitals between 1980 and 2009. The overall survival rate, the spectrum of histopathological diagnosis and their associated prognostic significance were investigated. RESULTS: The study group consisted of 30 men and 24 women with a median age of 60.3 years. Histopathological analysis revealed the following: usual interstitial pneumonia (UIP), 15 cases; nonspecific interstitial pneumonia/fibrosis, 16 cases; organizing pneumonia, 4 cases; unclassifiable, 2 cases; desquamative interstitial pneumonia, 1 case; and bronchiolar disease, 16 cases. In survival outcome, 10 yr survival rate was 76.6%. Patients with UIP had significantly worse prognosis than those with non-UIP (RLD cases except those with UIP) (p = 0.0452). CONCLUSION: RLD includes several histopathological groups. Patients with UIP have worse survival than those with other types of RLD. Histopathological diagnosis may have a major impact on prognostication in patients with RLD.

Effect of switching from salmeterol/fluticasone to formoterol/ budesonide combinations in patients with uncontrolled asthma.

BACKGROUND: Combination therapy with an inhaled corticosteroid (ICS) and a long-acting ß(2)-agonist (LABA) in a single inhaler is the mainstay of asthma management and salmeterol/fluticasone combination (SFC) and fixed-dose formoterol/budesonide combination (FBC) are currently available in Japan; however, there is nothing to choose between the two. The purpose of this study was to clarify the effect of switching from SFC to FBC in patients with asthma not adequately controlled under the former treatment regimen. METHODS: This was a prospective, multicenter, open-label, uncontrolled longitudinal study in 87 adult patients with an Asthma Control Questionnaire, 5-item version (ACQ5) score of greater than 0.75 under treatment with SFC 50/250µg one inhalation twice daily (bid). SFC was switched to FBC 4.5/160µg two inhalations bid. Study outcomes included ACQ5 score, peak expiratory flow (PEF), FEV(1), and fractional exhaled nitric oxide (FeNO) at the end of treatment period. RESULTS: Eighty-three patients completed the study. ACQ5 scores improved and exceeded the clinically meaningful difference after 12 weeks of treatment and well-controlled asthma (ACQ5 score ≤0.75) was attained in 37 (44.6%) patients. Minimum and maximum PEF and FEV(1) values improved significantly, but not FeNO values, after switching from SFC to FBC. CONCLUSIONS: Switching ICS/LABA combination therapy is a useful option in the management of asthma that is not optimally controlled.

Nonspecific interstitial pneumonia: prognostic significance of high-resolution computed tomography in 59 patients.

OBJECTIVE: To retrospectively analyze the prognostic implications of high-resolution computed tomography (HRCT) findings for patients with biopsy-proven nonspecific interstitial pneumonia (NSIP). METHODS: Fifty-nine patients with NSIP (25 idiopathic NSIP, 34 collagen-vascular disease-associated NSIP) were included. Two chest radiologists independently evaluated the extent, presence, and distribution of various HRCT findings. Cox hazards analysis was used to evaluate the relationship between HRCT findings and prognosis. RESULTS: The 5-year survival rate was 83% and the 10-year survival rate was 66%. Univariate analysis revealed that the extent of areas with ground-glass attenuation without traction bronchi-bronchiolectasis and that of airs-pace consolidation were associated with favorable outcome, whereas that of intralobular reticular opacities was associated with worse prognosis. Multivariate analysis showed that the extent of air-space consolidation was an independent factor of favorable outcome. CONCLUSION: In NSIP, the extent of areas with ground-glass attenuation without traction bronchi-bronchiolectasis, air-space consolidation, and intralobular reticular opacities correlate with survival.

Phase II study of erlotinib as third-line monotherapy in patients with advanced non-small-cell lung cancer without epidermal growth factor receptor mutations.

OBJECTIVE: There are few standard therapeutic options beyond second-line treatment. We aimed to evaluate the efficacy and safety of erlotinib monotherapy as third-line chemotherapy in patients with advanced non-small-cell lung cancer without epidermal growth factor receptor mutations. METHODS: In this phase II trial, patients who did not have epidermal growth factor receptor mutations and who had previously received two cytotoxic chemotherapy regimens containing platinum were treated with erlotinib (150 mg, per os) until disease progression or unacceptable toxicity. RESULTS: Twenty patients were eligible for the assessment of efficacy and safety. Three cases showed a partial response, and eight cases showed stable disease with an overall response rate of 15.0% (95% confidence interval: 5.2-36.0%) and a disease control rate of 55.0% (95% confidence interval: 34.2-74.2%). Median progression-free survival and overall survival time were 2.1 and 6.7 months, respectively. Although dose reduction was required in one patient because of skin toxicity, grade 3/4 toxicity or pulmonary disease was not observed. CONCLUSIONS: Erlotinib as third-line therapy showed an acceptable response rate, survival time and toxicity. It could be a potential third-line therapy for patients without epidermal growth factor receptor mutations.

[A case of resected pulmonary mucormycosis that was suspected of mixed infection with Aspergillus fumigatus, diagnosed by transbronchial lung biopsy].

A 73-year-old man was admitted with high fever and right chest pain. Chest X-ray showed a rapidly growing mass shadow in the right lower lung field. The patient had been in remission for malignant lymphoma and had developed interstitial pneumonia and diabetes mellitus following 1 year of corticosteroid therapy. His illness was diagnosed as invasive aspergillosis because of a high level of beta-D-glucan and cultured Aspergillus fumigatus in the sputum. He was treated with a combination of micafungin and itraconazole. However, because these agents did not improve his clinical condition, transbronchial lung biopsy was performed. Histologically, Mucor hyphae were detected in these specimens. Micafungin and itraconazole were stopped and infusion of liposomal amphotericin B was initiated. Because his condition worsened, a right lower lobectomy was performed. Rhizopus Oryzae was detected in the lung tissue. We report a case of pulmonary mucormycosis in which mixed infection with A. fumigatus was suspected. Pulmonary mucormycosis is a life-threatening infection in which it is rare that an antemortem diagnosis is established and organisms are isolated. We believe diagnostic tests should be performed aggressively, even when pulmonary aspergillosis is suspected.

Distinct prognosis of idiopathic nonspecific interstitial pneumonia (NSIP) fulfilling criteria for undifferentiated connective tissue disease (UCTD).

BACKGROUND: Although idiopathic nonspecific interstitial pneumonia (NSIP) was initially identified as a provisional diagnosis, the 2008 American Thoracic Society Project concluded that idiopathic NSIP is a distinct form of idiopathic interstitial pneumonia. However, an association between idiopathic NSIP and autoimmune diseases still attracts interest. In this context, a recent study proposed an intriguing concept that idiopathic NSIP is the pulmonary manifestation of undifferentiated connective tissue disease (UCTD). However, this has not been confirmed in a large number of patients with idiopathic NSIP. The present study was conducted to investigate the proportion and characteristics of patients with idiopathic NSIP who meet the criteria for UCTD. METHODS: We reviewed 47 consecutive patients with idiopathic NSIP and examined whether they met prespecified criteria for UCTD. Furthermore, we compared the clinical characteristics between patients fulfilling the UCTD criteria (UCTD-NSIP) and those not meeting them (Non-UCTD-NSIP). RESULTS: Of 47 patients with idiopathic NSIP, 22 (47%) met the UCTD criteria. Common symptoms associated with connective tissue diseases (CTDs) were skin change (50%) and Raynaud's phenomenon (41%) in UCTD-NSIP. UCTD-NSIP showed a female predominance and significantly higher percentages of lymphocytes with a lower CD4/CD8 ratio in bronchoalveolar lavage than Non-UCTD-NSIP. Interestingly, UCTD-NSIP had a significantly better survival than Non-UCTD-NSIP. CONCLUSIONS: Idiopathic NSIP included subjects who fulfilled the UCTD criteria, and these subjects had different clinical characteristics with significantly better outcome than those who did not meet the criteria. These data suggest that a part, but not all, of patients with idiopathic NSIP show CTD-like features with a distinct prognosis.

[Clinical case study of lung cancer accompanied by pulmonary aspergillosis].

We retrospectively studied clinical cases of lung cancer complicated by pulmonary aspergillosis. A total of 19 cases with average age of 69.5 years were encountered over the last 9 years. All had a history of smoking and 18 were men. In 2 cases, pulmonary aspergillosis and lung cancer were diagnosed concurrently. Pulmonary aspergillosis was diagnosed first in 4 cases and lung cancer was diagnosed first in 13 cases, in 11 of which pulmonary aspergillosis developed after surgery for lung cancer. In the non-operated group 5 cases had complications at the same site and 3 had complications at a different site. In the operated group, 10 cases subsequently had ipsilateral pulmonary aspergillosis and 1 case had contralateral pulmonary aspergillosis. Thirteen cases received antifungal medication. Lung cancer therapy is a risk factor for pulmonary aspergillosis. Careful medication is recommended.

Phase II study of combination chemotherapy with S-1 and weekly cisplatin in patients with previously untreated advanced non-small cell lung cancer.

We aimed to evaluate the efficacy and safety of combination chemotherapy with S-1 and low-dose weekly cisplatin in patients with advanced non-small cell lung cancer (NSCLC). In this phase II trial, previously untreated patients with stage IIIB/IV NSCLC were treated with oral administration of S-1 at 80 mg/m(2) for 21 days and three consecutive weekly low doses of cisplatin (25 mg/m(2)) followed by a 2-week rest period. Twenty-six patients were eligible for the assessment of efficacy and safety. Six partial responses were observed with an overall response rate of 23.1% (95% confidence interval: 12.3-31.6%). The median survival time and median progression-free survival were 13.4 months and 5.4 months, respectively. Grade 3/4 hematologic toxicities were observed in 9 patients (34.6%), including one grade 4 neutropenia and thrombocytopenia. As for non-hematologic adverse reactions, although grade 3 events were observed in 4 patients (15.3%), no severe renal toxicity or vomiting was found. S-1 and weekly low-dose cisplatin combination chemotherapy in patients with advanced NSCLC showed an acceptable response rate, overall survival time, and toxicity. Because this regimen can be performed in an outpatient setting, it might be an alternative useful and convenient option. Further investigations with a large population are required to confirm our results.

[A case of endobronchial lesion due to infection with Mycobacterium intracellulare].

A 53-year-old man was hospitalized in April 2001 because of left cervical lymphadenopathy and a mass shadow in the left lingular segment. Bronchoscopy revealed an elevated lesion in the left main bronchus, but a biopsy showed no specific findings. A left cervical lymph node biopsy revealed lymphoid hyperplasia only and no malignancy. After the patient was discharged, bronchial irrigation solution from the left lingular segment was found to be positive for Mycobacterium intracellulare. In July 2001 the shadow in the left lingular segment had worsened, and bronchoscopy was performed again. This revealed ulceration in the left main bronchus and edematous narrowing of the bronchial lumen at the opening of the lingular segment. A granulated lesion accompained by severe inflammation was seen in a biopsied specimen taken from the same site. Bronchial lesion induced by an acid-fast-stain positive nontuberculosis mycobacteria was noted. Treatment with rifampicin (RFP), clarithromycin (CAM), ethambutol (EB), and streptomycin (SM) was started, but a rash most likely caused by RFP developed, and RFP was replaced by ciprofloxacin (CPFX). The treatment was continued and symptoms improved. Since non-tuberculous mycobacteriosis accompanied with bronchial lesions is rare, a case report was made.

[A case of pulmonary epithelioid hemangioendothelioma detected on medical checkup].

A 51-year-old woman was admitted to our hospital because of bilateral multiple nodular shadows detected on a medical checkup chest X-ray film. Video-assisted thoracoscopic biopsy and hematoxylin eosin staining showed protrusion of the polypoid tumor tissue into the alveolar lumina, and the centers of nodules were occupied by hyalinized matrices. Immunohistochemical stain demonstrated that tumor cells were positive for factor VIII-related antigen, CD-34, and vimentin. The tumor was therefore diagnosed as pulmonary epithelioid hemangioendothelioma (PEH). PEH usually grows slowly. Standard therapy for PEH has not yet been established. We have followed the patient for 2 years without any treatment, but no symptoms have appeared.

[Successful treatment with cyclosporine in a case of progressive interstitial pneumonia associated with systemic sclerosis].

A 55-year-old man was admitted to our hospital with dyspnea on effort and sclerodactyly. The chest radiograph showed reticulonodular shadows in both lower lung fields. A diagnosis of systemic sclerosis was made based on the characteristic skin lesions, interstitial pneumonia and the positivity for anti-Scl-70 antibody. Surgical biopsies were performed, which showed various features characteristic of organizing pneumonia and non-specific interstitial pneumonia. Prednisolone and cyclophosphamide were given to the patient, but clinical symptoms and chest radiographic findings worsened. After cyclophosphamide was replaced with cyclosporine, his symptoms, chest radiographic findings and pulmonary function improved and stabilized. It is suggested that cyclosporine is useful for the treatment of progressive interstitial pneumonia associated with systemic sclerosis.