Current Issue : July - September Volume : 2017 Issue Number : 3 Articles : 6 Articles
Background: Asthma is characterized by a heterogeneous inflammatory profile and can be subdivided into\nT(h)2-high and T(h)2-low airway inflammation. Profiling of a broader panel of airway cytokines in large unselected\npatient cohorts is lacking.\nMethods: Patients (n = 205) were defined as being ââ?¬Å?cytokine-low/highââ?¬Â if sputum mRNA expression of a particular\ncytokine was outside the respective 10th/90th percentile range of the control group (n = 80). Unsupervised\nhierarchical clustering was used to determine clusters based on sputum cytokine profiles.\nResults: Half of patients (n = 108; 52.6%) had a classical T(h)2-high (ââ?¬Å?IL-4-, IL-5- and/or IL-13-highââ?¬Â) sputum cytokine\nprofile. Unsupervised cluster analysis revealed 5 clusters. Patients with an ââ?¬Å?IL-4- and/or IL-13-highââ?¬Â pattern\nsurprisingly did not cluster but were equally distributed among the 5 clusters. Patients with an ââ?¬Å?IL-5-, IL-17A-/F- and\nIL-25- highââ?¬Â profile were restricted to cluster 1 (n = 24) with increased sputum eosinophil as well as neutrophil\ncounts and poor lung function parameters at baseline and 2 years later. Four other clusters were identified:\nââ?¬Å?IL-5-high or IL-10-highââ?¬Â (n = 16), ââ?¬Å?IL-6-highââ?¬Â (n = 8), ââ?¬Å?IL-22-highââ?¬Â (n = 25). Cluster 5 (n = 132) consists of patients\nwithout ââ?¬Å?cytokine-highââ?¬Â pattern or patients with only high IL-4 and/or IL-13.\nConclusion: We identified 5 unique asthma molecular phenotypes by biological clustering. Type 2 cytokines cluster\nwith non-type 2 cytokines in 4 out of 5 clusters. Unsupervised analysis thus not supports a priori type 2 versus\nnon-type 2 molecular phenotypes. www.clinicaltrials.gov NCT01224938. Registered 18 October 2010...
Background: Asthma patients are enrolled in multimodal pulmonary rehabilitation (PR) programs. However,\navailable data for the effectiveness of PR in asthma are sparse. Therefore, the primary aim of this randomized\ncontrol trial (RCT) is to evaluate short-term (end of rehabilitation) and intermediate-term effectiveness (3 months\nafter rehabilitation) of PR for patients with asthma regarding asthma control (primary outcome) and other\noutcomes. Secondly, moderator effects of gender, age, baseline asthma control, quality of life, and anxiety will be\nexamined. Thirdly, a longitudinal follow-up study will explore the course of the outcomes over one year and the\nannual costs.\nMethods: The EPRA study is a single-center randomized controlled waiting-list trial in the Bad Reichenhall Clinic.\nInclusion criteria include a referral diagnosis for uncontrolled asthma, no cognitive impairment and no very severe\nco-morbidities that indicate significantly greater illness morbidity than asthma alone. In the intervention group (IG),\nparticipants will start PR within 4 weeks after randomization; participants of the control group (CG) will start PR 20\nweeks after randomization. Data will be assessed at randomization (T0), after 4 weeks (T1; IG: begin of PR), 7 weeks\n(T2; IG: end of PR), and 20 weeks (T3, CG: begin of PR). The primary outcome is asthma control at T2/T3. Secondary\noutcomes are health-related quality of life, functional exercise capacity, dyspnea, anxiety, depression, subjective selfmanagement\nskills, illness perceptions, sick leave and subjective work ability. Outcomes will be analyzed with\nanalysis of covariance, including baseline values of the respective outcomes as covariates. Healthcare costs will be\nanalyzed with a gamma model with a log-link.\nA longitudinal follow-up study will generate additional data at 3/6/9/12 months after PR for both IG and CG. Latent\nchange models will be used to analyze the course of the primary and secondary outcomes. Annual cost differences\nbefore and after rehabilitation will be compared by paired t-test.\nDiscussion: This RCT will determine the effectiveness of a complex inpatient PR for asthma patients concerning\nasthma control. Furthermore, important medical and economic information regarding the effectiveness of PR as\npart of the long-term management of patients with uncontrolled asthma will be generated....
Background: In a previous study, 6-minute walk distance (6MWD) improvement with sildenafil was not dose dependent\nat the 3 doses tested (20, 40, and 80 mg 3 times daily [TID]). This study assessed whether lower doses were less effective\nthan the approved 20-mg TID dosage.\nMethods: Treatment-naive patients with pulmonary arterial hypertension were randomized to 12 weeks of double-blind\nsildenafil 1, 5, or 20 mg TID; 12 weeks of open-label sildenafil 20 mg TID followed. Changes from baseline in 6-minute\nwalk distance (6MWD) for sildenafil 1 or 5 mg versus 20 mg TID were compared using a Williams test. Hemodynamics,\nfunctional class, and biomarkers were assessed.\nResults: The study was prematurely terminated for non-safety reasons, with 129 of 219 planned patients treated. At week\n12, 6MWD change from baseline was significantly greater for sildenafil 20 versus 1 mg (P = 0.011) but not versus 5 mg. At\nweek 24, 6MWD increases from baseline were larger in those initially randomized to 20 versus 5 or 1 mg (74 vs 50 and\n47 m, respectively). At week 12, changes in hemodynamic parameters were generally small and variable between\ntreatment groups; odds ratios for improvement in functional class were not statistically significantly different.\nImprovements in B-type natriuretic peptide levels were significantly greater with sildenafil 20 versus 1 but not 5 mg.\nConclusions: Sildenafil 20 mg TID appeared to be more effective than 1 mg TID for improving 6MWD; sildenafil 5 mg\nTID appeared to have similar clinical and hemodynamic effects as 20 mg TID....
Background: Long-term oxygen therapy (LTOT) is the only component of the management of chronic obstructive\npulmonary disease (COPD) that improves survival in patients with severe daytime hypoxemia. LTOT is usually provided\nby a stationary oxygen concentrator and is recommended to be used for at least 15ââ?¬â??18 h a day. Several studies have\ndemonstrated a deterioration in arterial blood gas pressures and oxygen saturation during sleep in patients with COPD,\neven in those not qualifying for LTOT. The suggestion has been made that the natural progression of COPD to its end\nstages of chronic pulmonary hypertension, severe hypoxemia, right heart failure, and death is dependent upon the\nseverity of desaturation occurring during sleep. The primary objective of the International Nocturnal Oxygen (INOX)\ntrial is to determine, in patients with COPD not qualifying for LTOT but who present significant nocturnal arterial\noxygen desaturation, whether nocturnal oxygen provided for a period of 3 years decreases mortality or delay the\nprescription of LTOT.\nMethods: The INOX trial is a 3-year, multi-center, placebo-controlled, randomized trial of nocturnal oxygen therapy\nadded to usual care. Eligible patients are those with a diagnosis of COPD supported by a history of past smoking and\nobstructive disease who fulfill our definition of significant nocturnal oxygen desaturation (i.e., ââ?°Â¥ 30% of the recording\ntime with transcutaneous arterial oxygen saturation < 90% on either of two consecutive recordings). Patients allocated\nin the control group receive room air delivered by a concentrator modified to deliver 21% oxygen. The comparison is\ndouble blind. The primary outcome is a composite of mortality from all cause or requirement for LTOT. Secondary\noutcomes include quality of life and utility measures, costs from a societal perspective and compliance with oxygen\ntherapy. The follow-up period is intended to last at least 3 years.\nDiscussion: The benefits of LTOT have been demonstrated whereas those of nocturnal oxygen therapy alone have\nnot. The INOX trial will likely determine whether supplemental oxygen during sleep is effective in reducing mortality,\ndelaying the need for LTOT and improving health-related quality of life in patients with COPD who desaturate overnight....
Background: Little is known about the mechanistic basis for the exercise intolerance characteristic of patients with\nrespiratory disease; a lack of clearly defined, distinct patient groups limits interpretation of many studies. The purpose\nof this pilot study was to investigate the pulmonary oxygen uptake (V_: O2) response, and its potential determinants, in\npatients with emphysema and idiopathic pulmonary fibrosis (IPF).\nMethods: Following a ramp incremental test for the determination of peak V_: O2 and the gas exchange threshold, six\nemphysema (66 Ã?± 7 years; FEV1, 36 Ã?± 16%), five IPF (65 Ã?± 12 years; FEV1, 82 Ã?± 11%) and ten healthy control participants\n(63 Ã?± 6 years) completed three repeat, heavy-intensity exercise transitions on a cycle ergometer. Throughout each\ntransition, pulmonary gas exchange, heart rate and muscle deoxygenation ([HHb], patients only) were assessed\ncontinuously and subsequently modelled using a mono-exponential with (V_: O2, [HHb]) or without (HR) a time delay.\nResults: The V_: O2 phase II time-constant (Ãâ??) did not differ between IPF and emphysema, with both groups significantly\nslower than healthy controls (Emphysema, 65 Ã?± 11; IPF, 69 Ã?± 7; Control, 31 Ã?± 7 s; P < 0.05). The HR Ãâ?? was slower in\nemphysema relative to IPF, with both groups significantly slower than controls (Emphysema, 87 Ã?± 19; IPF, 119 Ã?± 20;\nControl, 58 Ã?± 11 s; P < 0.05). In contrast, neither the [HHb] Ãâ?? nor [HHb]:O2 ratio differed between patient groups.\nConclusions: The slower V_: O2 kinetics in emphysema and IPF may reflect poorer matching of O2 delivery-to-utilisation.\nOur findings extend our understanding of the exercise dysfunction in patients with respiratory disease and may help to\ninform the development of appropriately targeted rehabilitation strategies....
Introduction. Failure of the vascular pulmonary remodeling at birth often manifests as pulmonary hypertension (PHT) and is\nassociated with a variety of neonatal lung disorders including a uniformly fatal developmental disorder known as alveolar capillary\ndysplasia with misalignment of pulmonary veins (ACD/MPV). Serumserotonin regulation has been linked to pulmonary vascular\nfunction and disease, and serotonin transporter (SERT) is thought to be one of the key regulators in these processes.We sought to\nfind evidence of a role that SERT plays in the neonatal respiratory adaptation process and in the pathomechanism of ACD/MPV.\nMethods.We used histology and immunohistochemistry to determine the timetable of SERT protein expression in normal human\nfetal and postnatal lungs and in cases of newborn and childhood PHT of varied etiology. In addition, we tested for a SERT gene\npromoter defect in ACD/MPV patients. Results.We found that SERT protein expression begins at 30 weeks of gestation, increases\nto term, and stays high postnatally. ACD/MPV patients had diminished SERT expression without SERT promoter alteration.\nConclusion. We concluded that SERT/serotonin pathway is crucial in the process of pulmonary vascular remodeling/adaptation\nat birth and plays a key role in the pathobiology of ACD/MPV....
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