Efficacy of inhaled N-acetylcysteine monotherapy in patients with early stage idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a fatal disorder for which there are currently no specific or effective medical treatments. A multicentre, prospective, randomized, controlled clinical trial was conducted to assess the efficacy of inhaled N-acetylcysteine (NAC) monotherapy in Japanese patients with early stage IPF. METHODS: Eligible patients had well-defined IPF of mild-to-moderate severity, with no desaturation on exercise. Of 100 patients screened, 76 were randomly assigned to an NAC treatment group (group A; n = 38) that received 352.4 mg of NAC by inhalation twice daily or to a control group (group B; n = 38) that received no therapy. The primary endpoint was the change from baseline in forced vital capacity (FVC) at 48 weeks. RESULTS: There were no significant overall differences in the change in FVC between groups A and B. Post hoc exploratory analyses showed that NAC therapy was associated with stability of FVC in (i) a subset of patients with initial FVC <95% of predicted (n = 49; difference in FVC decline 0.12 L; P = 0.02) and (ii) in patients with initial diffusing capacity of carbon monoxide <55% of predicted (n = 21; difference in FVC decline 0.17 L; P = 0.009). CONCLUSIONS: These findings indicate that NAC monotherapy may have some beneficial effect in patients with early stage IPF. Further trials in more select IPF populations with progressive disease are required to prove the efficacy of inhaled NAC.

[A case of yellow nail syndrome with bilateral pleural effusion].

A 68-year-old woman, suffering from dyspnea on exertion, was admitted to our hospital. She had noticed her nails become yellow 8 years previously. She had mild bilateral effusion. Examination of the pleural fluid revealed exudates which were lymphocyte-rich, a high concentration of adenosine deaminase (ADA) and elevated serum levels of soluble interleukin-2 receptors. These confirmed the diagnosis of yellow nail syndrome.

[High-sensitivity C-reactive protein and changes over time in forced expiratory volume in 1 second in adult-onset asthma].

PURPOSE: To study the possibility that changes in high-sensitivity C-reactive protein (hs-CRP) may be a predictor of forced expiratory volume in 1 second (FEV1) decline over time in adult asthmatic subjects. METHODS: Subjects with adult-onset asthma with no smoking history underwent complete medical evaluation at Yoka Public Hospital in both 2005 and in 2008 (n = 26). We analyzed the correlation between hs-CRP levels and FEV1 changes over time, in relation to whether or not they received inhaled corticosteroid (ICS) therapy. We also measured the cardio-ankle vascular index (CAVI), intima-media-thickness (IMT), and fraction of exhaled nitric oxide (FeNO) of hospital staff members who acted as non ICS asthmatic subjects (n = 11), and also performed multiple regression analysis. RESULTS: In the non-ICS asthmatic subjects group (n = 19), there was a significant correlation between log (hs-CRP) levels and FEV1 changes (R = -0.734, P < 0.001). After controlling for age, body mass index, CAVI, IMT, and FeNO, hs-CRP was found to be an independent risk factor. CONCLUSION: Hs-CRP levels are a predictor of FEV1 decline over time in adult-onset asthmatic patients with no smoking history, who are not receiving ICS therapy.

[A case of ANCA-associated vasculitis with diffuse alveolar hemorrhage successfully treated by plasmapheresis].

A 65-year-old man was admitted due to rapidly progressing dyspnea experienced over a 3-day period. Chest radiography and computed tomography conducted upon admission showed diffuse bilateral interstitial infiltrate. Bronchoalveolar lavage fluid contained blood and siderophores, which suggested pulmonary alveolar hemorrhage. Laboratory data showed that the serum MPO-ANCA level was elevated, and so ANCA-associated pulmonary hemorrhage was diagnosed. Although aggressive immunosuppressive agents were administered, including steroids and cyclophosphamides, the patient's condition worsened. Plasmapheresis using fresh frozen plasma was performed on day 5, after which his symptoms improved dramatically. Plasmapheresis was done 6 times, and the pulmonary lesions resolved. The patient was discharged 6 months later. This case report suggests that plasmapheresis may be an effective treatment for ANCA-associated vasculitis with diffuse alveolar hemorrhage that is resistant to aggressive immunosuppressive therapy.

[A case of pulmonary aspergillosis accompanied with eosinophilic pneumonia].

An infiltrative shadow was observed in the upper lobe of the left of a 60-year-old man lung during the course of paroxysmal tachycardia. Fever and coughing occurred one month later, and ground-glass opacities (GGOs) were found extensively in the lower left lung field. Although his condition strongly suggested allergic bronchopulmonary aspergillosis (ABPA) due to significantly increased eosinophil count in the peripheral blood and bronchoalveolar lavage fluid of the lower lobe of the left lung, anti-aspergillus antibody precipitation, and positive immediate intradermal test, the Rosenberg diagnostic criteria for ABPA were not satisfied. He was given a diagnosis of eosinophilic pneumonia, and GGO disappeared when itraconazole and prednisolone were administered. However, since the shadow in the upper lobe of the left lung later increased and percutaneous thoracocentesis revealed the presence of Aspergillus fumigatus, prednisolone treatment was discontinued and micafungin was administered. Nonetheless, the shadow spread into both lungs and regardless of treatment with amphotericin-B, the patient died. Although the present case is different from a typical ABPA, it indicates that allergic reaction can be induced by Aspergillus infection in the lung field, apart from the central airway. In addition, the development of an appropriate therapeutic strategy against both infection and allergy in such cases is essential.

Intrabronchial Infusion of Autologous Blood Plus Thrombin for Intractable Pneumothorax After Bronchial Occlusion Using Silicon Spigots: A Case Series of 9 Patients With Emphysema.

BACKGROUND: Bronchial occlusion therapy using silicon spigots is effective for intractable pneumothorax. However, sometimes the pneumothorax is refractory to bronchial occlusion because of collateral ventilation. For such difficult pneumothoraces, we attempted an intrabronchial infusion of autologous blood plus thrombin to control collateral ventilation and stop air leaks. METHODS: We performed bronchial occlusions using silicon spigots in patients with spontaneous pneumothorax secondary to emphysema and refractory to chest drainage, but which was inoperable owing to each patient's poor surgical candidacy and poor overall health condition. When bronchial occlusion proved ineffective, we undertook intrabronchial infusion of autologous blood plus thrombin, 2 to 4 days after bronchial occlusion. A catheter was inserted into the subpleural area, through a gap between the silicon spigot and the bronchial wall, using a flexible bronchoscope under fluoroscopic guidance. Autologous blood, followed by a thrombin solution, was infused using the catheter. We repeated the same infusion a total of 4 to 6 times while changing the target bronchi. All interventions were performed under local anesthesia. RESULTS: The subjects were 9 men, aged from 61 to 88 years, with smoking histories. Three patients also had interstitial pneumonia, and 6 patients had undergone pleurodesis in vain before bronchial occlusion. For 4of the 9 patients, autologous blood plus thrombin infusions successfully stopped air leaks, and in 3 patients, intrabronchial infusions and pleurodesis halted leaks altogether. CONCLUSION: Intrabronchial infusion of autologous blood plus thrombin was effective for intractable pneumothoraces that could not be clinically managed, even by bronchial occlusion using silicon spigots.

IgG4-related disease in asbestos-related pleural disease.

A 67-year-old man with a history of asbestos exposure and rounded atelectasis complained of cough and swelling in the left submandibular region. Computed tomography showed an increase in size of the right lower lung lobe lesion, which was recognized as the pre-existing rounded atelectasis, as well as swelling of the pancreas and submandibular glands. Biopsy from a submandibular gland and the pulmonary lesion led to a diagnosis of immunoglobulin G4-related disease (IgG4-RD). IgG4-RD is a recently recognized disease that was first reported as an autoimmune disease; however, some reports have indicated another pathogenesis of an allergic nature that is characterized by type 2 helper T cell (Th2) inflammation. Additionally, it is recognized that long-term exposure to asbestos can cause immune dysregulation. Here we present a case of IgG4-RD associated with asbestos-related pleural disease. Asbestos-induced immune dysregulation may be one etiology of IgG4-RD.

Effects of bronchoscopic lung volume reduction using transbronchial infusion of autologous blood and thrombin in patients with severe chronic obstructive pulmonary disease.

BACKGROUND: Existing medical treatments have limitations in the management of very severe chronic obstructive pulmonary disease (COPD). METHODS: We performed bronchoscopic lung volume reduction (BLVR) using transbronchial infusion of autologous blood and thrombin (BLVR with blood) in three patients with very severe COPD whose dyspnea could not be relieved by maximum medical management. Two patients underwent BLVR with blood in the left and right lungs at intervals of a half-year or a year, and one patient underwent this procedure in only the right lung. We assessed the changes in pulmonary function, exercise capacity and quality of life before and after BLVR with blood in a total of five procedures. RESULTS: The subjects were 58- to 74-year-old males. Their forced expiratory volume in one second (FEV1) percent predicted ranged from 14.8% to 23.4%. BLVR with blood achieved significant improvements as follows (values before → after the procedure, mean ± standard deviation): FEV1 0.45r the L → 0.76r the L (P=0.004), inspiratory capacity 1.50cityo L → 2.05±.05c L (P=0.015), 3-minute walk test 46.8nuteo m → 89.6±34.5 m (P=0.004). Lung function peaked several months after BLVR with blood and returned to nearly the baseline level in 6 months, but exercise capacity was better than that at baseline for at least 12 months. St. George's Respiratory Questionnaire (SGRQ), measured in two patients before and 12 months after the procedure, showed remarkable improvements (-15.6 and -11.9 units). CONCLUSIONS: BLVR with blood is an effective palliative treatment for very severe COPD.

Nontuberculous mycobacterial lung disease accompanied by organizing pneumonia.

We herein report our experience with patients who had nontuberculous mycobacterial lung disease (NTM disease) accompanied by organizing pneumonia (OP). Out of 98 NTM disease patients who had undergone a biopsy or surgical resection, 11 patients had OP that was revealed histologically. After excluding six patients who had OP-related diseases (idiopathic interstitial pneumonia, rheumatoid arthritis, etc.), the remaining five patients were studied. Two of them (a 73-year-old man and a 66-year-old woman) showed common clinical feature: acute-onset symptoms of cough and fever, infiltrating shadows and dramatic improvement following treatment with a corticosteroid and anti-mycobacterial therapy. Our cases demonstrate that NTM disease is sometimes accompanied by OP histologically, and some such cases show common clinical features.

Percutaneous needle washing for the diagnosis of pulmonary thin-walled cavitary lesions filled with air.

OBJECTIVE: It is difficult to obtain sufficient material from pulmonary thin-walled cavitary lesions filled with air by conventional percutaneous aspiration biopsy in order to make a diagnosis. In these cases, we performed percutaneous needle washing (PNW) and ascertained the diagnostic significance of this method. MATERIALS AND METHODS: PNW was performed on 27 patients with a pulmonary thin-walled cavitary lesion whose diagnosis could not be made by sputum and bronchoscopic examinations. Before centesis, the depth of the lesion was measured on CT scan. After the 22-gauge needle was inserted under X-ray fluoroscopic guidance, normal saline was injected into the cavity and aspirated. The aspirated material was examined cytologically and microbiologically. The procedure was carried out during one 30-second breath-holding. RESULTS: Upon performing PNW on 27 patients, malignant cells were detected in 10 patients and a bacterial or fungal pathogen was detected in 9 other patients [Aspergillus (4), Mycobacterium (3), Staphylococcus (1), Streptococcus (1)]. The diagnoses of 16 of the 17 patients who were negative for malignant cells on PNW, were ascertained as benign disease during their clinical course including 3 patients who were diagnosed as (or suspected of) having infectious disease clinically, while the diagnosis of one case was unknown. Therefore, the diagnostic sensitivity of PNW for malignant diseases was 91% (10/11), while that for infectious diseases was 69% (9/13). Mild pneumothorax was the only complication of PNW (2 cases). CONCLUSION: PNW may be an appropriate diagnostic procedure for pulmonary thin-walled cavitary lesions whose diagnosis can not be established by other techniques.

Prognostic significance of the lymphocyte-to-neutrophil ratio in percutaneous fine-needle aspiration biopsy specimens of advanced nonsmall cell lung carcinoma.

BACKGROUND: The prognostic significance of tumor-infiltrating lymphocytes (TILs) in surgically resected carcinomas was reported. To apply this to inoperable nonsmall cell lung carcinomas (NSCLC) of Stage IIIB-IV, the authors estimated the occurrence of TILs using percutaneous fine-needle aspiration biopsy specimens, and tested the validity of this method. METHODS: The authors defined the L-N index as [L(S)/(L(S) + N(S)) - L(B)/(L(B) + N(B))], in which L(S) and N(S) denoted lymphocyte and neutrophil counts in the aspiration smear, and L(B) and N(B) denoted lymphocyte and neutrophil counts in the peripheral blood specimen. The cutoff value was set at twice the standard deviation of the L-N index of 41 smears contaminated with abundant blood. Retrospectively, the authors compared the survival rate of the group with a high L-N index (lymphocyte-dominant group) (n = 12) with the survival rate of the group with a low L-N index (lymphocyte-nondominant group) (n = 60). Then, they performed a prospective study and compared the survival rates of these 2 groups (n = 21 and n = 54). The Cox proportional hazards model was used to determine the effect of the L-N index as a continuous variable and other prognostic factors. The correlation (r) between the L-N index-based grouping (L-N grouping) and the histologic grade of TILs was studied among resected lung tumor specimens (n = 164). RESULTS: In the retrospective and prospective studies, the survival rate was significantly higher in the lymphocyte-dominant group than in the lymphocyte-nondominant group (P = 0.0019 and P = 0.0001). Using multivariate analysis, the L-N index was an independent prognostic factor. A significant correlation was noted between L-N grouping and histologic grade of TILs (r = 0.476). CONCLUSIONS: The L-N index of aspiration smears was found to be an independent prognostic factor for patients with advanced-stage NSCLC. L-N grouping was correlated with the histologic assessment of TILs.