Prevalence and clinical characteristics of earlobe crease in systemic sclerosis: Possible association with vascular dysfunction.

Patients with systemic sclerosis (SSc) develop various vasculopathy-induced vascular disorders such as Raynaud's phenomenon, abnormal nail-fold capillaries, persistent digital ischemia, digital ulcers (DU), and sometimes develop renal crisis and pulmonary artery hypertension (PAH), affecting prognosis. Earlobe crease (ELC), also known as Frank's sign, is a wrinkle extending from the tragus to the outer border of the earlobe and is generally recognized as the sign of cardiovascular events. However, no previous study analyzed the association between ELC and SSc. In this study, we examined the prevalence and clinical characteristics of ELC in SSc patients. We analyzed 145 Japanese SSc patients and found that the prevalence of ELC in SSc patients was 23.4% (43/145), similar to that previously reported in the general population without SSc. Using univariate analysis, we found that SSc patients with ELC were characterized by old age, high incidence of DU, ILD and PAH, and high complication of coronary artery diseases (CAD) compared with SSc patients without ELC. In multivariate analysis, ELC was significantly associated with old age and incidence of DU. PAH tended to correlate with ELC without statistical significance. These results suggest that ELC may be associated with vascular disorders in SSc patients. This is the first report concerning the prevalence and clinical characteristics of ELC in patients with SSc. ELC is very easy to detect in clinical practice and helps physicians to identify SSc patients at risk of developing vascular disorders such as DU and PAH.

Relationship between esophageal motility abnormalities and skin or lung involvements in patients with systemic sclerosis.

BACKGROUND: Esophageal motility abnormalities (EMAs) and interstitial lung diseases (ILDs) are often seen in patients with systemic sclerosis (SSc). Gastroesophageal reflux disease (GERD) could be associated with ILDs, but it is not fully understood if ILDs are caused by GERD or SSc itself. METHODS: A total of 109 patients with SSc who underwent high-resolution manometry were enrolled. Esophageal motility was diagnosed with the Chicago classification v3.0. The severity of skin thickness was evaluated by the modified Rodnan total skin thickness score (mRSS). The severity of ILDs was assessed with the chest high-resolution computer tomography (HRCT) scoring system. Relationships between EMAs, GERD, autoantibodies, skin thickness and ILDs were evaluated. RESULTS: 44 patients had normal esophageal motility, eight had esophago-gastric junction outflow obstruction, one had distal esophageal spasm, 27 had ineffective esophageal motility and 29 had absent contractility (AC). Patients with AC had more GERD than those with normal esophageal motility (p < 0.05). The mRSS score in patients with AC was significantly higher than that in those with normal esophageal motility (p < 0.05). The HRCT score in patients with AC tended to be higher than that in those with normal esophageal motility (p = 0.05). A multivariable analysis showed that severe skin thickness was a significant predictor of AC. GERD was not a significant predictor for ILDs. CONCLUSIONS: There were significant correlations between EMAs and severe skin thickness. GERD is not an etiology of ILDs.

Alendronate inhalation ameliorates elastase-induced pulmonary emphysema in mice by induction of apoptosis of alveolar macrophages.

Alveolar macrophages play a crucial role in the pathogenesis of emphysema, for which there is currently no effective treatment. Bisphosphonates are widely used to treat osteoclast-mediated bone diseases. Here we show that delivery of the nitrogen-containing bisphosphonate alendronate via aerosol inhalation ameliorates elastase-induced emphysema in mice. Inhaled, but not orally ingested, alendronate inhibits airspace enlargement after elastase instillation, and induces apoptosis of macrophages in bronchoalveolar fluid via caspase-3- and mevalonate-dependent pathways. Cytometric analysis indicates that the F4/80(+)CD11b(high)CD11c(mild) population characterizing inflammatory macrophages, and the F4/80(+)CD11b(mild)CD11c(high) population defining resident alveolar macrophages take up substantial amounts of the bisphosphonate imaging agent OsteoSense680 after aerosol inhalation. We further show that alendronate inhibits macrophage migratory and phagocytotic activities and blunts the inflammatory response of alveolar macrophages by inhibiting nuclear factor-κB signalling. Given that the alendronate inhalation effectively induces apoptosis in both recruited and resident alveolar macrophages, we suggest this strategy may have therapeutic potential for the treatment of emphysema.

Effects of inhaled tiotropium plus transdermal tulobuterol versus tiotropium alone on impulse oscillation system (IOS)-assessed measures of peripheral airway resistance and reactance, lung function and quality of life in patients with COPD: a randomized crossover study.

BACKGROUND: The addition of transdermal tulobuterol (Tulo) to inhaled tiotropium bromide (Tio) produced beneficial effects on spirometry-assessed parameters of respiratory function, disease-related symptoms and quality of life in patients with chronic obstructive pulmonary disease (COPD). AIM: To compare the effects of Tio plus Tulo versus Tio alone on peripheral airway obstruction and quality of life in Japanese patients with COPD using impulse oscillation system (IOS)-assessed measures. PATIENTS AND METHODS: Patients aged 50-80 years with clinically stable COPD and a forced expiratory volume in 1 s (FEV(1)) that was 30-80% of the predicted value were randomized to receive Tio 18 µg once daily, or combination therapy with Tio 18 µg once daily plus Tulo 2 mg once daily for 4 weeks. Patients then switched treatments for a further 4 weeks. RESULTS: Sixteen patients completed the study. Tio plus Tulo was associated with significantly greater improvements than Tio in IOS-assessed markers of resistance (R5 and R5-R20), reactance and reactance area, from baseline to week 4. Both treatments significantly improved these markers over the 4-week treatment period, with the exception of R20 for which improvements were not significant. Tio plus Tulo improved symptoms of dyspnea to a significantly greater extent than Tio alone. St. George's Respiratory Questionnaire Score-Total was not significantly different between the two groups, but improvement from baseline in the 'impact' component was significantly greater with Tio plus Tulo than with Tio alone. CONCLUSIONS: Coadministration of transdermal Tulo with inhaled Tio, as well as Tio alone, is associated with beneficial effects on IOS-assessed measures of peripheral airway obstruction in patients with COPD.