Cough-reflex sensitivity to inhaled capsaicin in COPD associated with increased exacerbation frequency

Background and objective:   The causes of exacerbations in COPD patients are poorly understood. This study examined the association between cough-reflex sensitivity in patients with stable COPD and the frequency of subsequent exacerbations.
Methods:   The sampling frame for cases and controls for this study was patients attending a hospital outpatient clinic. cough-reflex sensitivity was evaluated using the log concentration of capsaicin causing five or more coughs (log C₅). Subsequent COPD exacerbations were identified prospectively via symptom-based diaries over a 12-month period.
Results:   The study group comprised 45 COPD subjects and 10 controls. Mean log C₅ was lower in the COPD group than in the control group (0.97 (95% confidence interval (CI): 0.76–1.18) versus 1.26 (95% CI: 0.81–1.71), P  = 0.095). In the COPD group, log C₅ was negatively correlated with serum CRP level ( r  = −0.36, P  = 0.02) and significantly associated with the exacerbation frequency ( r  = −0.38, P  = 0.01). Stepwise multiple regression analysis showed that cough-reflex sensitivity was significantly associated with exacerbation frequency ( r ² = 0.15, P  = 0.01).
Conclusions:   Hypersensitivity of the cough reflex to inhaled capsaicin might reflect airway inflammation in stable COPD patients, which predisposes to frequent exacerbations.     

Effects of KF19514, a Phosphodiesterase 4 and 1 Inhibitor,on Bronchial Inflammation and Remodeling in a Murine Model of Chronic Asthma

BackgroundPhosphodiesterase 4 selective inhibitor may prevent airway inflammation and remodeling.ObjectiveThe aim of this study was to investigate the effects of KF19514, a phosphodiesterase 4 and 1 dual inhibitor, on chronic airway inflammation and remodeling following chronic exposure to aerosolized antigen in mice.MethodsOvalbumin (OVA) was administered intraperitoneally to BALB/c mice on days 0 and 14, and the mice were then exposed to aerosolized OVA daily for 4 weeks. Twenty-four hours following the final inhalation, bronchial responsiveness to acetylcholine was measured, and histologic examination and hydroxyproline content of the lung were evaluated.ResultsBronchial responsiveness to acetylcholine, number of inflammatory cells and eosinophils in the lamina propria, thickness of epithelial and subepithelial collagen layers, and hydroxyproline content of the lung increased following chronic exposure to OVA for 7 weeks. KF19514 significantly prevented all of these changes.ConclusionsPhosphodiesterase 4 and 1 inhibitors such as KF19514 may help prevent bronchial hyperresponsiveness and chronic asthma-induced airway remodeling.     

Thioredoxin-1 suppresses systemic inflammatory responses against cigarette smoking

Thioredoxin-1 (TRX) is a small redox-active protein with antioxidative effects and redox-regulating functions. Cigarette smoking is a major etiological factor in the pathogenesis of a variety of diseases and recruits systemic immune and inflammatory responses. This report demonstrates that TRX attenuates the systemic inflammatory responses induced by cigarette smoking. The mRNA expressions of tumor necrosis factor alpha (TNF-alpha) and macrophage migration inhibitory factor (MIF) were suppressed in the spleen of TRX overexpressing transgenic mice (TRX-tg) exposed to cigarette smoking, compared with control C57BL/6 mice. In addition, protein carbonylation, a marker of cellular protein oxidation, was enhanced by cigarette smoking in the tissues of heart and liver in control mice more than in TRX-tg mice. These findings suggest that TRX may suppress the systemic inflammatory responses against cigarette smoking.     

Mitochondrial Delivery of Bongkrekic Acid Using a MITO-Porter Prevents the Induction of Apoptosis in Human HeLa Cells

The fact that mitochondrial dysfunction has been implicated in a variety of human diseases suggests that they would be expected as a target organelle for these diseases. Bongkrekic acid (BKA) is a chemical that functions as a ligand of the adenine nucleotide translocator and is known to potently inhibit the mitochondrial permeability transition that is associated with apoptosis. Thus, delivering it to mitochondria would be an innovative therapy for the treatment of mitochondrial diseases that are largely associated with apoptosis. Here, we report on the use of a MITO-Porter, an innovative nanocarrier for mitochondrial delivery via mitochondrial membrane fusion, for delivering BKA to mitochondria. We first constructed a BKA-MITO-Porter, in which BKA is contained in lipid envelopes of a MITO-Porter. We then confirmed that the BKA–MITO-Porter was efficiently internalized into cells and is delivered to mitochondria, similar to a conventional MITO-Porter. Moreover, we evaluated the antiapoptosis effect of the BKA–MITO-Porter in HeLa cells by measuring caspase 3/7 activity. The findings confirmed that the BKA–MITO-Porter showed a strong antiapoptosis effect compared with naked BKA. The results reported here demonstrate its potential for the use in therapies aimed at mitochondrial diseases, as a mitochondrial medicine candidate. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1008–1015, 2013     

Regional differences in the prevalence of sensitization to environmental allergens: Analysis on IgE antibody testing conducted at major clinical testing laboratories throughout Japan from 2002 to 2011

BackgroundIdentification of sensitized allergens for patients with respiratory allergy is an important step in disease care and environmental allergen control. The Japanese archipelago belongs to various climate categories due to its length from north to south which transverse the subarctic in the north to the subtropical in the south, suggesting substantial regional differences in dominant environmental allergens. However, few studies have assessed the regional differences in the prevalence of sensitization to environmental allergens.MethodsWe requested three major clinical testing laboratories to provide us with summarized results of antigen-specific IgE-antibody (Ab) measurements. These measurements were collected for clinical purposes throughout Japan from 2002 through 2011. The prevalence of positivity for IgE-Ab against 19 environmental allergens was calculated for each prefecture in order to evaluate regional differences.ResultsTest data on specific IgE-Ab of 19,969,753 orders were analyzed. The prevalence of positivity for house dust mites was high and the regional difference was low, whereas apparent regional differences were found for pollen, insects, and fungi. The prevalence of positivity for Japanese cedar was low in Hokkaido and Okinawa, while those to alder was highest in Hokkaido. Higher prevalence for insects was observed in southern areas (Okinawa and prefectures in Kyusyu).ConclusionsFindings of this study clearly demonstrated regional differences in the prevalence of sensitization to environmental allergens in Japan and the study also provides useful information for the clinician when deciding which allergens should preferentially be measured for IgE-Ab after considering regional difference.     

Risk factors for falls and fractures at night in relation to lower urinary tract symptoms: a survey of outpatients and inpatients at a general hospital

We investigated potential risk factors, including factors related to lower urinary tract symptoms (LUTS), for falls and fractures at night among outpatients and inpatients in a general hospital, via a questionnaire. The questionnaire included items to record the age, sex, number of consulting doctors, history of 11 particular medical diseases, LUTS, sleep, and falls and fractures at night. We distributed the questionnaire to 1,334 patients 51 years old or older in our hospital. Of the questionnaires completed, 96.9% were valid for analysis. Multivariate analyses revealed that "drinking water before bedtime or while in bed" was the strongest risk factor (odds ratio＝7.499) for bone fractures while "postural syncope" was the strongest risk factor (odds ratio＝5.041, except past medical history) for falls. In terms of LUTS, urge incontinence was a significant risk factor for falls.     

Relationship between swallowing function and breathing/phonation

Objective

Clarification of the association between the swallowing function and respiratory and phonatory functions.