Current Issue : January - March Volume : 2015 Issue Number : 1 Articles : 7 Articles
Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a long-term complication following an\nacute pulmonary embolism (PE). It is frequently diagnosed at advanced stages which is concerning as delayed\ntreatment has important implications for favourable clinical outcome. Performing a follow-up examination of\npatients diagnosed with acute PE regardless of persisting symptoms and using all available technical procedures\nwould be both cost-intensive and possibly ineffective. Focusing diagnostic procedures therefore on only symptomatic\npatients may be a practical approach for detecting relevant CTEPH.\nThis study aimed to evaluate if a follow-up program for patients with acute PE based on telephone monitoring of\nsymptoms and further examination of only symptomatic patients could detect CTEPH. In addition, we investigated the\nrole of cardiopulmonary exercise testing (CPET) as a diagnostic tool.\nMethods: In a prospective cohort study all consecutive patients with newly diagnosed PE (n=170, 76 males, 94 females\nwithin 26 months) were recruited according to the inclusion and exclusion criteria. Patients were contacted via\ntelephone and asked to answer standardized questions relating to symptoms. At the time of the final analysis 130\npatients had been contacted. Symptomatic patients underwent a structured evaluation with echocardiography, CPET\nand complete work-up for CTEPH.\nResults: 37.7%, 25.5% and 29.3% of the patients reported symptoms after three, six, and twelve months respectively.\nSubsequent clinical evaluation of these symptomatic patients saw 20.4%, 11.5% and 18.8% of patients at the respective\nthree, six and twelve months time points having an echocardiography suggesting pulmonary hypertension (PH).\nCTEPH with pathological imaging and a mean pulmonary artery pressure (mPAP) ? 25 mm Hg at rest was\nconfirmed in eight subjects. Three subjects with mismatch perfusion defects showed an exercise induced\nincrease of PAP without increasing pulmonary artery occlusion pressure (PAOP). Two subjects with pulmonary\nhypertension at rest and one with an exercise induced increase of mPAP with normal PAOP showed perfusion\ndefects without echocardiographic signs of PH but a suspicious CPET.\nConclusion: A follow-up program based on telephone monitoring of symptoms and further structured evaluation\nof symptomatic subjects can detect patients with CTEPH. CPET may serve as a complementary diagnostic tool....
Background: The 6-minute walk test (6MWT) is used to measure exercise capacity and assess prognosis in interstitial\nlung disease (ILD). Although the 6MWT is usually considered to be a test of submaximal exercise capacity in ILD, the\nphysiological load imposed by this test is not well described and 6MWT outcomes are poorly understood. This study\naimed to compare cardiorespiratory responses to 6MWT and cardiopulmonary exercise test (CPET) in people with ILD.\nMethods: 47 participants with ILD (27 idiopathic pulmonary fibrosis (IPF), mean age 71 (SD 12) years, diffusing capacity\nfor carbon monoxide (TLCO) 49(15) %predicted) undertook CPET and 6MWT on the same day in random order.\nOxygen uptake (VO2), ventilation (VE) and carbon dioxide production (VCO2) were assessed during each test using a\nportable metabolic cart.\nResults: The VO2peak during the 6MWT was lower than during CPET (1.17(0.27) vs 1.30(0.37) L.min?1, p=0.001),\nrepresenting an average of 94% (range 62-135%) of CPET VO2peak. Achieving a higher percentage of CPET VO2peak on\n6MWT was associated with lower TLCO %predicted (r = ?0.43, p = 0.003) and more desaturation during walking (r = ?0.46,\np = 0.01). The VEpeak and VCO2peak were significantly lower during 6MWT than CPET (p < 0.05). However, participants\ndesaturated more during the 6MWT (86(6)% vs 89(4)%, p < 0.001). The degree of desaturation was not affected by the\npercent of peak VO2 achieved during the 6MWT. Responses were similar in the subgroup with IPF.\nConclusions: On average, the 6MWT elicits a high but submaximal oxygen uptake in people with ILD. However\nthe physiological load varies between individuals, with higher peak VO2 in those with more severe disease that\nmay match or exceed that achieved on CPET. The 6MWT is not always a test of submaximal exercise capacity in\npeople with ILD....
Background: Air pollution has many negative health effects on the general population, especially children, subjects\nwith underlying chronic disease and the elderly. The aims of this study were to evaluate the effects of traffic-related\npollution on the exacerbation of asthma and development of respiratory infections in Italian children suffering\nfrom asthma or wheezing compared with healthy subjects and to estimate the association between incremental\nincreases in principal pollutants and the incidence of respiratory symptoms.\nMethods: This prospective study enrolled 777 children aged 2 to 18 years (375 with recurrent wheezing or asthma\nand 402 healthy subjects). Over 12 months, parents filled out a daily clinical diary to report information about\nrespiratory symptoms, type of medication used and healthcare utilization. Clinical data were combined with the\nresults obtained using an air pollution monitoring system of the five most common pollutants.\nResults: Among the 329 children with recurrent wheezing or asthma and 364 healthy subjects who completed\nfollow-up, children with recurrent wheezing or asthma reported significantly more days of fever (p = 0.005) and\ncough (p < 0.001), episodes of rhinitis (p = 0.04) and tracheitis (p = 0.01), asthma attacks (p < 0.001), episodes of\npneumonia (p < 0.001) and hospitalizations (p = 0.02). In the wheezing/asthma cohort, living close to the street with\na high traffic density was a risk factor for asthma exacerbations (odds ratio [OR] = 1.79; 95% confidence interval [CI],\n1.13-2.84), whereas living near green areas was found to be protective (OR = 0.50; 95% CI, 0.31 -0.80). An increase of\n10 ?g/m3 of particulates less than 10 microns in diameter (PM10) and nitrogen dioxide (NO2) increased the onset\nof pneumonia only in wheezing/asthmatic children (continuous rate ratio [RR] = 1.08, 95% CI: 1.00-1.17 for PM10;\ncontinuous RR = 1.08, 95% CI: 1.01-1.17 for NO2).\nConclusions: There is a significant association between traffic-related pollution and the development of asthma\nexacerbations and respiratory infections in children born to atopic parents and in those suffering from recurrent\nwheezing or asthma. These findings suggest that environmental control may be crucial for respiratory health in\nchildren with underlying respiratory disease....
Background: Idiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung disease of unknown aetiology\nand poor prognosis, characterized by altered tissue repair and fibrosis. The extracellular matrix (ECM) is a critical\ncomponent in regulating cellular homeostasis and appropriate wound healing. The aim of our study was to\ndetermine the expression profile of highlighted ECM proteins in IPF lungs.\nMethods: ECM gene and protein expression was analyzed by cDNA microarrays, rt-PCR, immunohistochemistry and\nwestern-blot in lungs from idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), categorized as\nchronic (cHP) and subacute (saHP), and healthy lung tissue. Primary fibroblast cultures from normal subjects and\nfibrotic patients were studied to evaluate tenascin-C (TNC) synthesis.\nResults: A total of 20 ECM proteins were upregulated and 6 proteins downregulated in IPF. TNC was almost\nundetected in normal lungs and significantly upregulated in fibrotic lungs (IPF and cHP) compared to saHP.\nFurthermore, it was located specifically in the fibroblastic foci areas of the fibrotic lung with a subepithelial gradient\npattern. TNC levels were correlated with fibroblastic foci content in cHP lungs. Versican and fibronectin\nglycoproteins were associated with TNC, mainly in fibroblastic foci of fibrotic lungs. Fibroblasts from IPF patients\nconstitutively synthesized higher levels of TNC than normal fibroblasts. TNC and ?-sma was induced by TGF-?1 in\nboth fibrotic and normal fibroblasts. TNC treatment of normal and fibrotic fibroblasts induced a non-significant\nincreased ?-sma mRNA.\nConclusions: The difference in ECM glycoprotein content in interstitial lung diseases could contribute to the\ndevelopment of lung fibrosis. The increase of TNC in interstitial areas of fibrotic activity could play a key role in\nthe altered wound healing....
Background: Idiopathic pulmonary fibrosis (IPF) is a distinct form of interstitial pneumonia with unknown origin\nand poor prognosis. Current pharmacologic treatments are limited and lung transplantation is a viable option for\nappropriate patients. The aim of this review was to summarize lung transplantation survival in IPF patients overall,\nbetween single (SLT) vs. bilateral lung transplantation (BLT), pre- and post Lung Allocation Score (LAS), and\nsummarize wait-list survival.\nMethods: A systematic review of English-language studies published in Medline or Embase between 1990 and\n2013 was performed. Eligible studies were those of observational design reporting survival post-lung transplantation\nor while on the wait list among IPF patients.\nResults: Median survival post-transplantation among IPF patients is estimated at 4.5 years. From ISHLT and OPTN data,\none year survival ranged from 75% - 81%; 3-year: 59% - 64%; and 5-year: 47% - 53%. Post-transplant survival is lower for\nIPF vs. other underlying pre-transplant diagnoses. The proportion of IPF patients receiving BLT has steadily increased over\nthe last decade and a half. Unadjusted analyses suggest improved long-term survival for BLT vs. SLT; after adjustment for\npatient characteristics, the differences tend to disappear. IPF patients account for the largest proportion of patients on\nthe wait list and while wait list time has decreased, the number of transplants for IPF patients has increased over time.\nOPTN data show that wait list mortality is higher for IPF patients vs. other diagnoses. The proportion of IPF patients who\ndied while awaiting transplantation ranged from 14% to 67%. While later transplant year was associated with increased\nsurvival, no significant differences were noted pre vs. post LAS implementation; however a high LAS vs low LAS was\nassociated with decreased one-year survival.\nConclusions: IPF accounts for the largest proportion of patients awaiting lung transplants, and IPF is associated\nwith higher wait-list and post-transplant mortality vs. other diagnoses. Improved BLT vs. SLT survival may be the\nresult of selection bias. Survival pre- vs. post LAS appears to be similar except for IPF patients with high LAS,\nwho have lower survival compared to pre-LAS. Data on post-transplant morbidity outcomes are sparse....
Background: Acute respiratory distress syndrome (ARDS) is characterized by overwhelming inflammatory responses\nand lung remodeling. We hypothesized that leukocyte infiltration during the inflammatory response modulates\nepithelial remodeling through a mechanism of epithelial-mesenchymal transition (EMT).\nMethods: Human lung epithelial cells were treated for 30 min with hydrochloric acid (HCl). Human monocytes\nwere then cocultured with the epithelial cells for up to 48 h, in the presence or absence of blocking peptides\nagainst lymphocyte function-associated antigen-1 (LFA-1), or tyrphostin A9, a specific inhibitor for platelet-derived\ngrowth factor (PDGF) receptor tyrosine kinase.\nResults: Exposure of lung epithelial cells to HCl resulted in increased expression of intercellular adhesion\nmolecule-1 (ICAM-1) and production of interleukin (IL)-8 at 24 h. The expression of the epithelial markers E-cadherin\ndecreased while the mesenchymal markers vimentin and ?-smooth muscle actin (?-SMA) increased at 24 h and\nremained high at 48 h. The addition of monocytes augmented the profiles of lower expression of epithelial markers\nand higher mesenchymal markers accompanied by increased collagen deposition. This EMT profile was associated\nwith an enhanced production of IL-8 and PDGF. Treatment of the lung epithelial cells with the LAF-1 blocking\npeptides CD11a237ââ?¬â??246 or/and CD18112ââ?¬â??122 suppressed monocyte adhesion, production of IL-8, PDGF and\nhydroxyproline as well as EMT markers. Treatment with tyrphostin A9 prevented the EMT profile shift induced\nby HCl stimulation.\nConclusions: The interaction between epithelial cells and monocytes enhanced epithelial remodelling after initial\ninjury through EMT signalling that is associated with the release of soluble mediators, including IL-8 and PDGF...
Background: Bronchodilator medications are central to the symptomatic management of chronic obstructive\npulmonary disease (COPD). Metered-dose inhalers (MDIs) are the most commonly used devices to deliver treatment\nto patients with COPD and asthma, comprising approximately 70% of bronchodilator prescriptions. Proprietary\nporous-particle technology permits the formulation of long-acting muscarinic antagonists, long-acting ?2-agonists,\nand a combination of both in hydrofluoroalkane (HFA) MDIs, providing a solution to formulation challenges\ninherent to the development of HFA MDIs, which have contributed to the development of dry-powder inhalers.\nMethods: In this randomized, double-blind, 4-period, 6-treatment, placebo- and active-controlled, multicenter,\ncrossover study, 4 ascending single doses of a proprietary glycopyrronium (GP) MDI were evaluated compared with\nPlacebo MDI and open-label tiotropium (TIO) in study patients with COPD. Thirty-three study patients were enrolled\nand received single-dose administration of 4 of the 6 treatments (Placebo MDI, TIO 18 ?g, or GP MDI at 14.4, 28.8,\n57.6, and 115.2 ?g ex-actuator) with an interval of 1 to 3 weeks between doses. The primary efficacy endpoint was\npeak change in forced expiratory volume in 1 second (FEV1).\nResults: All 4 doses of GP MDI showed statistically superior efficacy compared with Placebo MDI for peak FEV1\n(differences of 146 to 248 mL; P < .001), with a clear dose ordering of the response. Statistically significant\ndifferences compared with Placebo MDI were noted at almost all doses for the secondary FEV1 parameters\n(P ? .049) except 24-hour trough FEV1 at 28.8 ?g. All doses were safe and well tolerated in this study; the most\nfrequently reported adverse event was dry mouth (0ââ?¬â??14.3% across doses; 9.5% for Placebo MDI, and 9.1% for TIO).\nConclusions: This study demonstrated superior bronchodilatory efficacy of GP MDI compared with Placebo MDI at\nall doses tested, and no serious adverse events were reported. This study supports the further evaluation of GP MDI\nin study patients with COPD. In addition, these findings indicate that the correct dosage of glycopyrronium is no\nmore than 115.2 ?g total daily dose, or 57.6 ?g twice daily based on comparisons with the active comparator....
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