Clinical significance of serum anti-GM-CSF autoantibody levels in autoimmune pulmonary alveolar proteinosis.

AIM: Precise clinical significance of antigranulocyte-macrophage colony stimulating factor (GM-CSF) autoantibody levels in autoimmune pulmonary alveolar proteinosis (aPAP) has not been well studied. METHODS: We obtained sera from 50 healthy controls, 46 aPAP patients, 50 with sarcoidosis, 52 with idiopathic interstitial pneumonia and 75 with pneumoconiosis. The clinical course of aPAP patients was assessed by scoring computed tomography images in 19 patients. RESULTS: The cut-off level of anti-GM-CSF IgG for discrimination between aPAP and other diffuse lung diseases was 2.8 µg/ml with 100% sensitivity and 98% specificity. Antibody levels at baseline were significantly lower in the improved group than in the unimproved group (p = 0.008). CONCLUSION: Our results indicate the existence of threshold levels of serum anti-GM-CSF IgG for the development and persistence of aPAP.

Interstitial Lung Disease after Pleurodesis for Malignant Pleural Effusion.

Objective Pleurodesis is an effective therapy for malignant pleural effusion (MPE). While interstitial lung disease (ILD) has been regarded as a serious complication of pleurodesis, its clinicopathological characteristics have not been fully understood. This study was conducted to elucidate the incidence of ILD and the risk factors for ILD in patients who underwent pleurodesis to control MPE. Methods The medical records of patients who underwent pleurodesis in Aichi Medical University between March 2008 and February 2013, the period before the approval of talc in Japan, were retrospectively analyzed. Results A total of 84 patients underwent pleurodesis, all using OK-432. ILD occurred in 13 patients (15.5%). The development of ILD after pleurodesis was significantly associated with old age (odds ratio [OR]: 4.82, 95% confidence interval [CI]: 1.22-19.08) and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment (OR: 5.97, CI: 1.7-20.9). A multivariate analysis revealed that >67 years of age (p=0.01) and EGFR-TKI treatment (p=0.02) were significantly associated with the development of pleurodesis-related ILD. Among the patients who received both pleurodesis and EGFR-TKIs (n=23), 8 patients developed ILD. All of these patients were receiving EGFR-TKI therapy at the time of pleurodesis or within 30 days after pleurodesis. In contrast, no cases of ILD were observed among the patients who stopped EGFR-TKIs before pleurodesis or started EGFR-TKIs at more than 30 days after pleurodesis. Conclusion ILD seemed to be a frequent complication of pleurodesis in patients using OK-432, especially elderly patients and those who underwent pleurodesis while receiving EGFR-TKI therapy or who started EGFR-TKI therapy within 30 days after pleurodesis.

The ATS/ERS/JRS/ALAT statement "IPF by HRCT" could predict acute exacerbation of interstitial lung disease in non-small cell lung cancer.

INTRODUCTION: Patients with non-small cell lung cancer (NSCLC) and interstitial lung disease (ILD) are at high risk of acute exacerbation of ILD (AE-ILD) when treated with systemic chemotherapy. Standard treatment for NSCLC complicated by ILD has not been established. PURPOSE AND METHODS: To examine whether the type of ILD categorized by the official ATS/ERS/JRS/ALAT statement as "idiopathic pulmonary fibrosis (IPF) by high-resolution computed tomography (HRCT)" could predict chemotherapy-induced AE-ILD in NSCLC patients with ILD, we retrospectively reviewed all patients with NSCLC complicated by ILD who had received chemotherapy at our institute from January 2007 until December 2013. Patients' characteristics, pathology and clinical staging of lung cancer, chemotherapy, type of ILD and AE-ILD during chemotherapy were evaluated. ILD was classified according to the statement as follows: usual interstitial pneumonia (UIP), possible UIP, and inconsistent with a UIP pattern. RESULTS: A total of 46 patients had pre-existing ILD and received chemotherapy. The mean age was 73 years (range 46-83 years). Fifteen (32.6%) of 46 patients with ILD developed chemotherapy-induced AE-ILD, which was seen more frequently in patients with ILD with a UIP pattern or possible UIP pattern than in patients with a pattern inconsistent with UIP (80% versus 9.7%, p<0.001). Multivariate analyses including age, sex, performance status and radiographic patterns of ILD showed that the presence of a UIP or possible UIP pattern was an independent risk factor for chemotherapy-induced AE-ILD. CONCLUSIONS: ILD with a UIP pattern or possible UIP pattern by the classification could be a risk factor for AE-ILD in NSCLC patients with ILD.

Therapeutic and preventive antiemetic effect of aprepitant in Japanese patients with thoracic malignancies who truly need it.

PURPOSE: Neurokinin-1 (NK-1) receptor antagonist is recommended for chemotherapy-induced nausea and vomiting (CINV) in highly emetogenic chemotherapy (HEC) and has recently been introduced to oncology practice in Japan. However, whether all patients undergoing HEC truly need NK-1 receptor antagonist remains unknown, and increasing medical costs due to uniform use of NK-1 receptor antagonist are a concern. This study was conducted to examine the prevalence of patients who needed aprepitant at the time of its introduction in Japan, and therapeutic and preventive effects of aprepitant on HEC or moderately emetogenic chemotherapy (MEC). PATIENTS AND METHODS: Eligible patients with thoracic malignancies who were to undergo HEC or MEC received 5-hydroxytryptamine receptor antagonists and dexamethasone to prevent CINV. Aprepitant was administered to treat CINV occurring in the first course, or to prevent CINV in the second course. Frequency of vomiting, degree of nausea, and quality of life with respect to CINV were assessed. RESULTS: In total, 96 patients were enrolled. Aprepitant was not administered in 57 and 88 % of patients who received HEC and MEC, respectively. In patients treated with aprepitant (n = 18), therapeutic use of aprepitant after occurrence of CINV (n = 9) decreased average scores in numerical rating scale for nausea from 7.44 to 5.44 (p = 0.10), and average frequency of vomiting per day from 2.11 to 0.11 (p = 0.03). Prophylactic use of aprepitant in the second course (n = 18) increased the proportion of patients with no significant nausea from 6 % (first course) to 50 % (second course; p = 0.007), and those with no vomiting from 33 to 89 % (p = 0.002). Aprepitant use also significantly improved quality of life with respect to CINV in the second course. CONCLUSION: More than half of patients receiving HEC and 88 % of patients receiving MEC did not use aprepitant. Aprepitant showed significant therapeutic and preventive effects on CINV in patients who truly needed it.

The efficacy of montelukast and airway mast cell profiles in patients with cough variant asthma.

BACKGROUND: Cough variant asthma (CVA) is characterized by chronic cough without apparent wheezing; its pathophysiology is considered to be similar to that of classic asthma. OBJECTIVE: The clinical effects of montelukast, a cysteinyl-leukotriene receptor antagonist, on cough variant asthma were assessed, and the activation profile of airway mast cells was examined. METHODS: Montelukast (10 mg/day) was given orally to 36 CVA patients (25 women and 11 men; median age, 37.5 years). Before treatment, the patients' bronchial mucosa underwent a biopsy with a fiberoptic bronchoscope. The biopsy specimens were double stained with anti-CD63 antibody and anti-human tryptase antibody. RESULTS: After 2 weeks of montelukast treatment, cough symptoms improved in 22 patients (the effective group) but did not improve in 14 patients (the ineffective group); in the ineffective group, the symptoms disappeared 2 weeks after they were switched to fluticasone propionate (400 microg/day) inhalation therapy. In the effective group, the time interval from the onset of symptoms to the initiation of treatment was significantly shorter than in the ineffective group. The bronchial mucosa biopsy specimens showed that the proportion of CD63-positive cells in tryptase-positive mast cells was significantly higher in the effective group than in the ineffective group; although the total numbers of mast cells were not different between the two groups. CONCLUSION: There is a subgroup of CVA patients in whom leukotrienes are closely involved in the pathogenesis of their chronic cough; activation of airway mast cells may be an essential feature in these patients.