An effective case of bronchoscopic balloon dilatation for tuberculous bronchial stenosis.

Endobronchial tuberculosis often causes bronchial stenosis. Balloon dilation is a minimally invasive and effective bronchoscopic intervention for bronchial stenosis; however, reports on balloon dilation in older individuals are limited. We present a case of a 77-year-old woman with endobronchial tuberculosis and clarify the efficacy and safety of balloon dilation. She presented with dyspnea, right lung atelectasis, and respiratory failure 55 days after initiation of antituberculosis therapy. We performed bronchoscopic balloon dilatation for the right main bronchial stenosis. Consequently, respiratory failure rapidly improved. Chest computed tomography (CT) showed improved lung atelectasis; however, severe bronchial stenosis and rhonchi persisted. Therefore, we performed a second balloon dilatation. CT 3 months after the first balloon dilation showed right upper bronchial stenosis and right lung middle lobe atelectasis. Restenosis was absent 21 months after third balloon dilatation. Bronchoscopic balloon dilation is effective for restenosis with repeated treatment and can be safely performed in older individuals.

Myelin oligodendrocyte glycoprotein antibody-associated disease in a patient with symptoms of aseptic meningitis who achieved spontaneous remission: A case report and review of the literature.

BACKGROUND: A few case reports have described patients with myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated demyelinating syndrome who presented with symptoms of aseptic meningitis. All such patients required immunotherapy. We report a patient with MOG-Ab-associated disorder (MOGAD) who presented with symptoms of aseptic meningitis and improved without treatment. CASE: A 13-year-old girl presented with fever, headache, decreased appetite, and neck stiffness. Cerebrospinal fluid (CSF) analysis revealed pleocytosis and magnetic resonance imaging (MRI) showed leptomeningeal enhancement. The patient was diagnosed with aseptic meningitis at admission. However, there were no signs of recovery 4 days after admission (i.e., 8 days after disease onset). Therefore, we performed extensive investigations to identify the cause of the underlying infection and inflammation. On day 14 after admission, the serum MOG-Ab test performed at admission came back positive (1:128) and she was diagnosed with MOGAD. She was discharged on day 18 after admission, because her symptoms, CSF pleocytosis, and MRI findings had improved. About 6 weeks after discharge, MRI revealed hyperintensity without gadolinium enhancement. However, her serum MOG-Ab test was negative. We did follow-ups for 11 months but found no new neurological symptoms. DISCUSSION AND CONCLUSION: To the best of our knowledge, this is the first ever report of a pediatric patient with MOGAD experiencing spontaneous remission with no demyelinating symptoms during an extended follow-up period.

Correlation between antibiotic use and antibiotic resistance: A multicenter study using the Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) system in Hokkaido, Japan.

BACKGROUND: The Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) system aggregates information related to antimicrobial resistance (AMR) measures in participating medical institutions nationwide and is intended to be used for promotion of AMR measures in participating facilities and their communities. This multicenter study aimed to determine the usefulness of the J-SIPHE system for evaluating the correlation between antibiotic use and antibiotic resistance in Hokkaido, Japan. METHODS: Data on antibiotic use and detection rate of major resistant Gram-negative bacteria at 19 hospitals in 2020 were collected from the J-SIPHE system, and data correlations were analyzed using JMP Pro. RESULTS: The detection rate of carbapenem-resistant Pseudomonas aeruginosa was significantly positively correlated with carbapenem use (Spearman's ρ = 0.551; P = .015). There were significant positive correlations between the detection rate of fluoroquinolone-resistant Escherichia coli and the use of piperacillin/tazobactam, carbapenems, and quinolones [ρ = 0.518 (P = .023), ρ = 0.76 (P < .001), and ρ = 0.502 (P = .029), respectively]. CONCLUSIONS: This is the first multicenter study to investigate the correlation between antibiotic use and antibiotic resistance using the J-SIPHE system. The results suggest that using this system may be beneficial for promoting AMR measures.

Kinetic changes in serum KL-6 levels predict disease progression in patients with systemic sclerosis-associated interstitial lung disease.

BACKGROUND: The clinical course of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) is highly variable. The Krebs von den Lungen-6 (KL-6) glycoprotein is a promising biomarker for reflecting epithelial injury. However, serum KL-6 and its association with the progression of SSc-ILD have been understudied. METHODS: We reviewed 77 consecutive patients with SSc-ILD seen from 2004 to 2016. A longitudinal study of forced vital capacity (FVC), serum KL-6 levels, and changes in KL-6 levels from baseline (ΔKL-6) was conducted. The progression of ILD was defined as ≥10% relative decline in FVC predicted or 5%-10% decline in FVC predicted along with radiological progression on chest computed tomography. The risk factors for ILD progression were assessed by univariate and multivariate regression. RESULTS: During a 5-year follow-up period, 10 (13%) patients showed rapid progression of ILD within 2 years, 39 (51%) showed overall progression during the 5 years, and 28 (36%) had stable disease. Most patients with progressive ILD showed elevations in serum KL-6 levels over the initial 1-year follow-up period. The best cut-off value for ΔKL-6 that predicted progression of ILD was 193 U/mL (sensitivity 81.6%, specificity 92.9%). Multivariate analysis adjusted by age, sex, smoking status, and immunosuppressant use found that diffuse cutaneous SSc (hazard ratio [HR] 4.51; 95% confidence interval [CI] 1.56-13.04) and ΔKL-6 > 193 U/mL from baseline (HR 7.19; 95% CI 3.30-15.69) were independent predictors for progression of SSc-ILD. CONCLUSION: Changes in the KL-6 level can be useful for predicting disease progression in patients with SSc-ILD.

Fractional analysis of bronchoalveolar lavage in systemic sclerosis-associated interstitial lung disease.

BACKGROUND: The utility of bronchoalveolar lavage (BAL) in the evaluation of systemic sclerosis-associated interstitial lung disease (SSc-ILD) remains controversial. Fractional analysis of BAL (FBAL) is a technique that can analyze small airways and alveolar compartments separately and has proven informative in other ILDs. The aim of this study was to explore FBAL characteristics across the spectrum of SSc-ILD severity. METHODS: We retrospectively reviewed patients with SSc-ILD who underwent bronchoscopy with FBAL using three 50 mL aliquots of saline solution. These aliquots were analyzed separately for differential cell composition (FBAL-1, -2, and -3). We compared the FBAL cell composition to the progression of ILD and end-stages of ILD using Cox proportional hazards models. RESULTS: Sixty-eight patients with SSc-ILD were enrolled in this study. The percentage of neutrophils and eosinophils was lower in FBAL-3 compared to FBAL-1. In contrast, the percentage of macrophages and lymphocytes was higher in FBAL-3. Neutrophils in FBAL-2, -3, and the estimated total FBAL cell fraction (FBAL-total) were negatively correlated with the forced vital capacity % predicted (r=-0.420, -0.362, -0.409, respectively). Although FBAL-total was not linked to the progression and end-stage of ILD, a high percentage of neutrophils in FBAL-3 was significantly associated with the development of end-stage ILD (HR 1.093, 95% CI: 1.003-1.190). CONCLUSIONS: A higher percentage of neutrophils in FBAL-3 is correlated with development of end-stage ILD in SSc-ILD as well as mortality.

Surfactant protein D: a useful marker for differentiation of drug-induced pneumonia and bacterial pneumonia.

BACKGROUND: Drug-induced pneumonia (d-pneumonia) and bacterial pneumonia (b-pneumonia) are often difficult to differentiate; therefore, this study examined the possibility of differentiating them using serum biomarkers. METHODS: The study included 22 and 16 patients diagnosed with b- and d-pneumonia, respectively, at our institution or affiliated institutions. For d-pneumonia, the causative drug was minocycline hydrochloride in four patients, gefitinib in two patients, nivolumab in two patients, pembrolizumab in two patients, sulfasalazine in two patients, loxoprofen in one patient, Bouiougitou in one patient, edoxaban tosilate hydrate in one patient, and abemaciclib in one patient. White blood cell (WBC), C-reactive protein (CRP), Krebs von den Lungen-6 (KL-6), surfactant protein (SP)-D, and SP-A levels were measured in each patient and compared between the groups. RESULTS: Significant differences were noted in the WBC and SP-D levels between the two groups (P < 0.05, P < 0.001), but not in the CRP, KL-6, or SP-A levels. CONCLUSION: The study results suggest that SP-D is a useful marker for differentiating b-pneumonia and d-pneumonia.

A case of retropharyngeal emphysema as a complication of pneumothorax.

Retropharyngeal emphysema is a rare condition, and it is important to determine whether the patient presents with complications including pneumomediastinum or other severe clinical presentations such as an upper airway obstruction. In such cases, patients should undergo urgent tracheostomy and surgical neck drainage with concurrent administration of broad-spectrum antibiotics.

IgG4-Related Pleuritis With No Other Organ Involvement.

A 65-year-old man was admitted for productive cough and dyspnea. Bilateral pleural effusions were observed on chest X-ray. Although the bilateral pleural effusions were exudative with an increased number of lymphocytes, bacterial culture and polymerase chain reaction analysis for Mycobacterium tuberculosis were negative. Immunological examinations showed high levels of immunoglobulin G4 (IgG4) in both serum and pleural effusion fluid. Pathologic evaluation of a left pleural biopsy specimen using hematoxylin and eosin staining and immunohistochemical staining showed fibrosis-associated lymphoplasmacytic infiltration, 50 IgG4-positive plasma cells per high-power field, and an IgG4/IgG ratio of 40%. Thus, a diagnosis of IgG4-related pleuritis without other systemic manifestations was established. The bilateral pleural effusion improved following corticosteroid therapy. This is a rare case of IgG4-related pleuritis with no other organ involvement.

Lung cancer in connective tissue disease-associated interstitial lung disease: clinical features and impact on outcomes.

BACKGROUNDS: Lung cancer (LC) adversely impacts survival in patients with idiopathic pulmonary fibrosis. However, little is known about LC in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). The aim of this study was to evaluate the prevalence of and risk factors for LC in CTD-ILD, and the clinical characteristics and survival of CTD-ILD patients with LC. METHODS: We conducted a single-center, retrospective review of patients with CTD-ILD from 2003 to 2016. Patients with pathologically diagnosed LC were identified. The prevalence, risk factors, and clinical features of LC and the impact of LC on CTD-ILD patient outcomes were observed. RESULTS: Of 266 patients with CTD-ILD, 24 (9.0%) had LC. CTD-ILD with LC was more likely in patients who were older, male, and smokers; had rheumatoid arthritis, a usual interstitial pneumonia pattern, emphysema on chest computed tomography scan, and lower diffusing capacity of the lung carbon monoxide (DLco)% predicted; and were not receiving immunosuppressive therapy. Multivariate analysis indicated that the presence of emphysema [odds ratio (OR), 8.473; 95% confidence interval (CI), 2.241-32.033] and nonuse of immunosuppressive therapy (OR, 8.111; 95% CI, 2.457-26.775) were independent risk factors for LC. CTD-ILD patients with LC had significantly worse survival than patients without LC (10-year survival rate: 28.5% vs. 81.8%, P<0.001). CONCLUSIONS: LC is associated with the presence of emphysema and nonuse of immunosuppressive therapy, and contributes to increased mortality in patients with CTD-ILD.

Antisynthetase syndrome: Pulmonary computed tomography findings of adult patients with antibodies to aminoacyl-tRNA synthetases.

OBJECTIVES: To describe the pulmonary CT findings in patients with anti-ARS-antibody-positive interstitial lung disease (anti-ARS-ILD) METHODS: The CT findings of 64 patients with anti-ARS-ILD were retrospectively reviewed. The images were retrospectively reviewed independently by 2 chest radiologists, and the final decision on the CT findings was made by a third chest radiologist. RESULTS: There were 16 male and 48 female patients, aged 54.2±13.4 years. Sixteen patients had anti Jo-1, 24 had anti-EJ, 9 had anti-PL-7, 7 had anti-PL-12, 5 had anti-KS, and 3 had anti-OJ antibodies. Overall, 63 patients (98.4%) had CT findings predominantly in the lower lobe; 61 patients (95.3%) showed peripheral opacities, and 47 patients (73.4%) showed peribronchovascular opacities. Ground-glass attenuation, consolidation, and reticulation showed similar distribution patterns. Regarding detailed CT findings, 89.1% of patients had lower volume loss, 76.6% had interlobular septal thickening, and 67.2% had thickening of bronchovascular bundles. The final radiologic diagnoses were as follows: inconsistent with usual interstitial pneumonia (UIP) in 63 patients (98.4%), which included nonspecific interstitial pneumonia (NSIP) in 35 patients (55.6%), organizing pneumonia (OP) in 4 patients (6.3%), and OP with fibrosis in 22 patients (34.9%). CONCLUSIONS: The characteristic CT findings of patients with anti-ARS-ILD were areas of ground-glass attenuation and reticulation, predominantly distributed as lower and peribronchovascular lesions, which is compatible with NSIP. One-third of patients showed OP with fibrosis.

A role for peripherally inserted central venous catheters in the prevention of catheter-related blood stream infections in patients with hematological malignancies.

Central venous catheter-related blood stream infections (CR-BSIs) are a serious complication in patients with hematological malignancies. However, it remains unclear whether there is a difference in the rate of CR-BSI associated with the conventional type of central venous catheters (cCVCs) and peripherally inserted CVCs (PICCs) in such patients. To address this question, we retrospectively investigated the incidence of CR-BSIs associated with PICCs versus cCVCs in patients with hematological malignancies. We used PICCs in all consecutive patients requiring CVC placement between February 2009 and February 2013. We compared the CR-BSI rate in patients with PICCs with that in patients with cCVCs treated between September 2006 and January 2009 (control group). Eighty-four patients received PICCs and 85 received cCVCs. The most common reason for removal due to catheter-related complications was CR-BSI. The CR-BSI rate in the PICC group was significantly lower than that in the cCVC group (PICCs: 1.23/1000 catheter days; cCVCs: 5.30/1000 catheter days; P < 0.01). Catheter-related complications other than CR-BSIs occurred at an extremely low rate in the PICC group. The median catheter-related complication-free survival duration was significantly longer in the PICC group than in the cCVC group. Our study shows that PICCs are useful in patients with hematological malignancies.

Electrophysiological characterization of human Na⁺/taurocholate cotransporting polypeptide (hNTCP) heterologously expressed in Xenopus laevis oocytes.

The Na(+)/taurocholate cotransporting polypeptide (NTCP) plays a major role in Na(+)-dependent bile acid uptake into hepatocytes. The purpose of the present study was to establish the heterologous expression of human NTCP (hNTCP) in Xenopus laevis oocytes and to elucidate whether the transport of bile acid via hNTCP is electrogenic using electrophysiological techniques. First, we evaluated the uptake of taurocholate (TCA) by hNTCP heterologously expressed in Xenopus oocytes utilizing [(3)H]-labeled TCA. The uptake of 1.2 µM TCA by cRNA-injected oocytes increased more than 100-fold compared to H2O-injected oocytes, indicating that hNTCP is robustly expressed in the oocytes. hNTCP-mediated transport of TCA is saturable with a Michaelis constant of 10.5 ± 2.9 µM. The Na(+)-activation kinetics describing the relationship between the concentration of Na(+) and the magnitude of the TCA uptake rate by hNTCP were sigmoidal with a Hill coefficient of 2.3 ± 0.4, indicating the involvement of more than one Na(+) in the transport process. Ntcp in primary cultured hepatocytes from rats exhibited similar Na(+)-activation kinetics of TCA uptake rate with a Hill coefficient of 1.9 ± 0.1, suggesting that hNTCP could be expressed properly in the oocytes and exhibit the electrogenic property of Na(+)-coupled TCA transport. The transport of TCA via hNTCP was subsequently determined in the oocytes by the inward currents induced via TCA uptake under voltage (-50 mV). Two hundred micromolar TCA induced significant inward currents that were entirely abolished by the substitution of Na(+) with N-methyl-d-glucamine (NMDG) in the perfusate, indicating that the TCA-induced currents were obligatorily dependent on the presence of Na(+). The TCA-induced currents were saturable, and the substrate concentration needed for half-maximal induction of the current was consistent with the Michaelis constant. Transportable substrates, such as rosuvastatin and fluvastatin, also induced currents. These results in the hNTCP heterologously expressed in Xenopus oocytes directly demonstrated that hNTCP is an electrogenic Na(+)-dependent transporter.

Pulmonary manifestations of anti-ARS antibody positive interstitial pneumonia--with or without PM/DM.

BACKGROUND: Autoantibodies against aminoacyl-tRNA synthetases (ARS) have been found to be highly specific for polymyositis and dermatomyositis (PM/DM) and to correlate strongly with complicating interstitial pneumonia (IP). The aim of the present study was to compare the clinical presentations of anti-ARS antibody-positive IP patients with or without manifestations of PM/DM. METHODS: We retrospectively examined 36 IP patients with anti-ARS antibodies. Sixteen patients presented with and 20 without the features of PM/DM. They were divided into PM/DM-IP and idiopathic-IP (IIP) groups. Clinical symptoms, findings on physical examination, laboratory data, pulmonary function, computed tomography (CT), and bronchoalveolar lavage fluid (BALF) cell counts were compared. RESULTS: Skin findings, myalgia, and elevation of serum creatinine kinase were found in the PM/DM-IP group. Features common to both groups included: volume loss in lower bilateral lobes; ground-glass opacities, reticular shadows and traction bronchiectasis on chest CT; high percentage of lymphocytes (IIP: 44.0% ± 21.0% (mean ± SD), PM/DM-IP: 50.5% ± 23.5%) and low CD4/8 ratios (IIP: 0.36 ± 0.34, PM/DM-IP: 0.44 ± 0.42) in BALF; decreased pulmonary function, including percentage of predicted vital capacity (VC) (IIP: 80.1% ± 15.4%, PM/DM-IP: 73.6% ± 16.4%), residual volume (RV) (IIP: 70.7% ± 21.7%, PM/DM-IP: 71.5% ± 17.1%), total lung capacity (TLC) (IIP: 73.4% ± 13.6%, PM/DM-IP: 71.6% ± 13.0%), and diffusing capacity DLco (IIP: 57.5% ± 26.7%, PM/DM-IP: 46.4% ± 10.3%). Both groups achieved good responses to initial corticosteroid or immunosuppressant therapy. CONCLUSION: Patients with anti-ARS antibody-positive IP have common pulmonary manifestations regardless of the presence of PM/DM.

The specific chymase inhibitor TY-51469 suppresses the accumulation of neutrophils in the lung and reduces silica-induced pulmonary fibrosis in mice.

Chymase is a chymotrypsin-like serine protease that is present in mast cells. Its activities include various effects associated with inflammatory responses. But little is known about the effects of chymase in pulmonary fibrosis. The mouse silicosis model was induced by intratracheal injection of 10 mg silica. The Ashcroft pathological score and the hydroxyproline content of lungs were measured to evaluate the effect of a chymase inhibitor, 2-[4-(5-fluoro-3-methylbenzo[b]thiophen-2-yl)sulfonamido-3-methanesulfonylphenyl] thiazole-4-carboxylic acid (TY-51469). The cellular composition and cytokine levels in bronchoalveolar lavage fluid (BALF) were also examined. Following TY-51469 treatment, the lung fibrosis score and hydroxyproline level were significantly reduced, and the number of neutrophils and the levels of macrophage inflammatory protein-2, monocyte chemoattractant protein-1, and transforming growth factor-ß1 in BALF were reduced on day 21. The administration of TY-51469 at an early stage showed a greater reduction of fibrosis compared to administration at a later stage. The neutrophil number in BALF in mice treated with TY-51469 both at an early stage and late stage was significantly reduced. The level of mouse mast cell proteinase-4 mRNA increased with time in silica-induced fibrosing lung tissue. These results show that the chymase inhibitor TY51469 suppresses the migration of neutrophils, which results in the suppression of lung fibrosis.

[A case of repeated bilateral pneumothorax associated with upper lobe predominant fibrosis in an aluminum processing worker].

A 39-year-old man, who had been working in an aluminum processing industry for 18 years, visited our hospital for right chest pain on March 2, 2007. A relapse of right pneumothorax was found, and he was hospitalized. As the pneumothorax did not improve with conservative treatment, video-assisted thoracoscopic biopsy and suturing of the right upper lobe were successfully performed. The pulmonary parenchyma had collapsed, there was pulmonary fibrosis, and lymphocytes had gathered in follicules. Based on elemental analysis results, we diagnosed aluminum lung. It was thought that overexpansion of the lower lobe with the predominant upper lobe fibrosis was caused by the aluminum deposition. We judged his condition to be serious and we started treatment with 25 mg/day prednisolone (PSL), and 120 mg/day cyclosporine (CyA). At the time of writing, he is an outpatient, and is being monitored on a regimen of 5 mg/day PSL and 160 mg/day CyA without any progression of pulmonary fibrosis or relapse of pneumothorax.

[Case of tuberculous bronchial stenosis followed-up by spirogram and successfully treated with a Dumon stent].

A 47-year-old man visited his family doctor because of chronic productive cough. Though there were no abnormal chest X-ray film findings, he was diagnosed as tuberculosis on the basis of a sputum examination. Therefore, he was introduced to our hospital and as tracheobronchial tuberculosis was diagnosed by the bronchofiberscopic findings, showing ulceration with a white nodules from the lower part of trachea to the left main bronchus. By treatment, the ulcer change was improved, but the left main bronchus narrowed to pinhole size. Furthermore, the flow-volume curve became worse, and stridor appeared. We inserted Dumon stent in the left main bronchus 4 months later. As a result, his symptoms and flow-volume curve were improved, and we removed the stent 4 years and 6 months later. In this valuable case, we could observe the progress of the post-tuberculosis bronchial stenosis respiratory physiologically.

Sputum eosinophilia, airway hyperresponsiveness and airway narrowing in young adults with former asthma.

BACKGROUND: 30-80% of outgrown asthma subjects develop symptoms again later in life. We investigated inflammation and function of lower airway in adolescents with former asthma. METHODS: 326 never-smoking young adults (mean age 24.0 years) were interviewed with special emphasis on history of asthma. Diagnosis of asthma was based on GINA guidelines. Former asthma subjects consisted of ones with a history of physician-diagnosed childhood asthma, who had been free of asthma symptoms without the use of medication for at least 10 years prior to the study. Provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second (FEV(1))(PC(20)) and eosinophil percentage in induced sputum were measured. RESULTS: 31 subjects were former asthma subjects (FBA), 11 subjects were current asthma subjects (CBA) and 284 subjects had no history of asthma (non-BA). PC(20) and FEV(1)/FVC ratio were significantly lower in the FBA group than in the non-BA group (P < 0.01). Maximal mid-expiratory flow (MMF) was significantly lower in the FBA group than in the non-BA group (P < 0.05). Sputum eosinophil percentage was significantly increased in the FBA group compared with the non-BA group (P < 0.01). PC(20) was significantly lower in the CBA group than in the FBA and non-BA groups (P < 0.01). FEV(1), FEV(1)/FVC ratio and MMF were significantly lower in the CBA group than in the FBA group (P < 0.05, P < 0.05 and P < 0.05, respectively) and the non-BA group (P < 0.01, P < 0.01 and P < 0.05, respectively). Sputum eosinophils were significantly higher in the CBA group than in the FBA and non-BA groups (P < 0.01). CONCLUSIONS: This study shows that subjects with long-term outgrown asthma continue to have airway eosinophilic inflammation, airway hyperresponsiveness and airway narrowing.

Angiotensin II type 2 receptor antagonist reduces bleomycin-induced pulmonary fibrosis in mice.

BACKGROUND: The role of angiotensin II type 2 receptor (AT2) in pulmonary fibrosis is unknown. To evaluate the influence of angiotensin II type 1 receptor (AT1) and AT2 antagonists in a mouse model of bleomycin (BLM)-induced pulmonary fibrosis. METHODS: We examined effects of the AT1 antagonist (AT1A) olmesartan medoxomil (olmesartan) and the AT2 antagonist (AT2A) PD-123319 on BLM-induced pulmonary fibrosis, which was evaluated by Ashcroft's pathological scoring and hydroxyproline content of lungs. We also analyzed the cellular composition and cytokine levels in bronchoalveolar lavage fluid (BALF). RESULTS: With olmesartan, the lung fibrosis score and hydroxyproline level were significantly reduced, and lymphocyte and neutrophil counts and tumor necrosis factor (TNF)-alpha levels in BALF were reduced on day 7. On day 14, macrophage and lymphocyte counts in BALF were reduced, accompanied by a reduction in the level of transforming growth factor (TGF)-beta1. With PD-123319, the lung fibrosis score and hydroxyproline level were reduced. On day 7, macrophage, lymphocyte, and neutrophil counts in BALF were reduced, accompanied by reductions in TNF-alpha and monocyte chemoattractant protein (MCP)-1 levels. On day 14, macrophage, lymphocyte, and neutrophil counts in BALF were also reduced, accompanied by a reduction in the level of macrophage inflammatory protein (MIP)-2 level but not TGF-beta1. CONCLUSION: Both AT1 and AT2 are involved in promoting interstitial pneumonia and pulmonary fibrosis via different mechanisms of action.

Exhaled nitric oxide levels in patients with atopic cough and cough variant asthma.

BACKGROUND AND OBJECTIVE: Atopic cough (AC) is an established clinical entity in Japan, in which patients present with a chronic persistent non-productive cough. Exhaled nitric oxide (NO) is a biomarker of eosinophilic airway inflammation. The present study examined whether exhaled NO levels were increased in AC in comparison with cough variant asthma (CVA) and bronchial asthma (BA). METHODS: Consecutive patients presenting with an isolated cough lasting at least 8 weeks were enrolled in the study. The aetiology of the chronic cough was determined according to the Japanese Respiratory Society guidelines for management of cough. Exhaled NO, capsaicin cough sensitivity (capsaicin concentration eliciting five or more coughs (C5)) and bronchial reversibility were measured at the patients' first visit. Bronchial responsiveness (PC20 to methacholine) was measured at their second visit following a 6-day course of bronchodilator therapy. RESULTS: There were 58 patients recruited and fully investigated; of these 9 and 11 patients were diagnosed with AC and CVA, respectively, as single causes of chronic cough. Ten patients with BA who had not received corticosteroid therapy in the previous 4 weeks and who attended the same clinic in the same time period acted as controls. Exhaled NO levels in patients with AC were significantly lower than those in patients with CVA and BA. There was no significant difference in the exhaled NO levels between patients with CVA and BA. CONCLUSIONS: Exhaled NO may reflect eosinophilic inflammation of peripheral airways and its measurement may be useful in differentiating CVA from AC and other causes of chronic non-productive cough.

Nonspecific interstitial pneumonia with abundant IgG4-positive cells infiltration, which was thought as pulmonary involvement of IgG4-related autoimmune disease.

Recently, great attention has been drawn to IgG4-related diseases such as autoimmune pancreatitis (AIP) sclerosing sialadenitis, retroperitoneum fibrosis, sclerosing cholangitis. IgG4-related diseases are characterized by high serum IgG4 concentrations, sclerosing inflammation with numerous IgG4-positive plasma cells, and steroid sensitivity irrespective of their organs of origin. In this report, we describe a case of nonspecific interstitial pneumonia, in which possible involvement of IgG4 was suggested. The patient was 59-year-old man, who was found to have bilateral interstitial pneumonia. Laboratory tests revealed that he had antinuclear antibody and a high serum IgG4 concentration. Pathological examination of the video-assisted thoracic surgery biopsy taken from the right lower lobe showed interstitial thickening associated with lymphoplasmacytic infiltration containing many IgG4-positive plasma cells. He was effectively treated by corticosteroid. The present case had many clinical and clinicopathologic similarities to systemic IgG4-related autoimmune disease. There have been no descriptions on isolated interstitial pneumonia with IgG4-positive plasma cell infiltration. This case suggested that IgG4-related disorders could also occur in the lung, and interstitial pneumonia may be a pulmonary manifestation of systemic IgG4-related autoimmune disease.