Doença pulmonar obstrutiva crônica

The chronic obstructive lung disease is reviewed with emphasys on its epidemiology and risk factors. The diagnosis, clinical aspects pulmonary, functional alterations and laboratorial findings are discussed. The treatment is also reviewed, based on the actual consensus, considering the following classes of approaches: bronchodilators, inhaled β-agonists, corticoids, methilxanthines, prolonged domiciliar-orygen therapy.

Fluticasone/formoterol dry powder versus budesonide/formoterol in adults and adolescents with uncontrolled or partly controlled asthma

This 12-week study compared the efficacy and safety of a fixed combination of fluticasone propionate plus formoterol (FL/F) 250/12 mu g b.i.d. administered via a dry powder inhaler (DPI) (Libbs Farmaceutica, Brazil) to a combination of budesonide plus formoterol (BD/F) 400/12 mu g b.i.d. After a 2-week run-in period (in which all patients were treated exclusively with budesonide plus formoterol), patients aged 12-65 years of age (N = 196) with uncontrolled asthma were randomized into an actively-controlled, open-labeled, parallel-group, multicentre, phase III study. The primary objective was to demonstrate non-inferiority, measured by morning peak expiratory flow (mPEF).The non-inferiority was demonstrated. A statistically significant improvement from baseline was observed in both groups in terms of lung function, asthma control, and the use of rescue medication. FL/F demonstrated a statistical superiority to BD/F in terms of lung function (FEV1) (p = 0.01) and for asthma control (p = 0.02). Non-significant between-group differences were observed with regards to exacerbation rates and adverse events.In uncontrolled or partly controlled asthma patients, the use of a combination of fluticasone propionate plus formoterol via DPI for 12-weeks was non-inferior and showed improvements in FEV1 and asthma control when compared to a combination of budesonide plus formoterol. (Clinical Trial number: ISRCTN60408425). (C) 2013 Elsevier Ltd. All rights reserved.

Formulation and nebulization of fluticasone propionate-loaded lipid nanocarriers.

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Inflammatory and functional effects of increasing asthma treatment with formoterol or double dose budesonide

Adding a long-acting beta(2)-agonist to inhaled corticosteroids (ICS) for asthma treatment is better than increasing ICS dose in improving clinical status, although there is no consensus about the impact of this regimen on inflammation. In this double-blind, randomized, parallel group study, asthmatics with moderate to severe disease used budesonide (400 mcg/day) for 5 weeks (run-in period); then they were randomized to use budesonide (800 mcg/day - BUD group) or budesonide plus formoterol (400 mcg and 24 mcg/day, respectively - FORMO group) for 9 weeks (treatment period). Home PEF measurements, symptom daily reporting, spirometry, sputum induction (for differential cell counts and sputum cell cultures), and hypertonic saline bronchial challenge test were performed before and after treatments. TNF-alpha, IL-4 and eotaxin-2 levels in the sputum and cell culture supernatants were determined. Morning and night PEF values increased in the FORMO group during the treatment period (p < 0.01), from 435 +/- 162 to 489 +/- 169 and 428 +/- 160 to 496 +/- 173 L/min, respectively. The rate of exacerbations in the FORMO group was lower than in the BUD group (p < 0.05). Neutrophil counts in sputum increased in both groups (p < 0.05) and leukocyte viability after 48 h-culture increased in the FORMO group (p < 0.05). No other parameter changed significantly in either group. This study showed that adding formoterol to budesonide improved home PEF and provided protection from exacerbations, although increase of leukocyte viability in cell culture may be a matter of concern and needs further investigation. (C) 2008 Elsevier Ltd. All rights reserved.

Suppression of Inflammatory Cytokine Secretion by an NF-kappa B Inhibitor DHMEQ in Nasal Polyps Fibroblasts

Background: NF-kappa B is an essential transcription factor strongly associated to inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP). DHMEQ is a NF-kappa B inhibitor that has been previously described with a greatpotential indecreasing inflammation in diseases other than CRSwNP. The aim of study isto evaluate the ability of DHMEQ to reducethe inflammatory recruiters on CRSwNP and to compare its anti-inflammatory profile as a single-agent or in association with fluticasone propionate (FP). Methods: nasal polyp fibroblasts were cultured in TNF-alpha enriched media. Cells were submitted to three different concentrations (1, 10 and 100nM) of either FP, DHMEQ or both. Inflammatory response was accessed by VCAM-1, ICAM-1 and RANTES expression (by RTQ-PCR) and protein levels by ELISA. Nuclear translocation of NF-kappa B was also evaluated. Results: both FP and DHMEQ inhibited inflammatory recruiters' production and NF-kappa B nuclear translocation. Interestingly, the anti-inflammatory effect from the association steroids plus DHMEQ was more intense than of each drug in separate. Conclusion: DHMEQ seems efficient in modulating the inflammatory process in CRSwNP. The synergic anti-inflammatory effect of DHMEQ and steroids may be a promising strategy to be explored, particularly in the setting of steroid-resistant NP. Copyright (c) 2012 S. Karger AG, Basel

Esophageal CandidiasisAn Adverse Effect of Inhaled Corticosteroids Therapy

Over the last few decades, inhaled corticosteroids (ICs) became the cornerstone in the treatment of persistent asthma. Their use improved asthma control, decreased mortality and also minimized adverse reactions associated with systemic steroid. Esophageal candidiasis is a rare complication resulting from the use of ICs. Although, in recent years, as their prescriptions has increased, more cases have been reported, especially in Japan. Listed are 4 case reports regarding esophageal candidiasis in asthmatic patients associated with inhaled budesonide administration. In the cases reported herein, the use of a different device of dry powder budesonide might have favored esophageal drug deposition and Candida infection. Patients denied using systemic corticosteroids in the previous 6 months. Furthermore, none of the patients presented Diabetes mellitus, malignant disease, HIV infection, or other immunosuppressive conditions. We conclude that patients treated with high doses of ICs are at higher risk of developing esophageal candidiasis. These patients should undergo upper gastrointestinal endoscopy whenever they present symptoms. Nevertheless, we must keep in mind that infection might also be asymptomatic and esophageal candidiasis prevalence may be higher than that reported thus far.

Liposomes and micro/nanoparticles as colloidal carriers for nasal drug delivery

The use of the nasal route for drug delivery has attracted much interest in recent years in the pharmaceutical field. Local and principally systemic drug delivery can be achieved by this route of administration. But the nasal route of delivery is not applicable to all drugs. Polar drugs and some macromolecules are not absorbed in sufficient concentration due to poor membrane permeability, rapid clearance and enzymatic degradation into the nasal cavity. Thus, alternative means that help overcome these nasal barriers are currently in development. Absorption enhancers such as phospholipids and surfactants are constantly used, but care must be taken in relation to their concentration. Drug delivery systems including liposomes, cyclodextrins, micro- and nanoparticles are being investigated to increase the bioavailability of drugs delivered intranasally. This review article discusses recent progress and specific development issues relating to colloidal drug delivery systems in nasal drug delivery. © 2006 Bentham Science Publishers Ltd.

Influence of treatment with intranasal corticosteroids on the nasal mucosa, weight, and corticosteroid concentration in rats

Background: The effect of intranasal corticosteroids on the nasal epithelium mucosa is an important parameter of treatment safety. This study was designed to examine whether treatment with topical corticosteroids in patients with allergic rhinitis causes atrophic nasal mucosal changes, when compared with systemic corticosteroids, in rats. Methods: Male Wistar rats were treated daily during 7 weeks with topical administration with 10 microliters of normal saline (control group), 10 microliters of mometasone furoate group, 10 microliters of triamcinolone acetonide (T group), and 8 mg/kg of daily subcutaneous injections of methylprednisolone sodium succinate (MP group). Body weight was evaluated weekly. At the end of the treatment, rats were killed by decapitation to collect blood for determination of corticosterone levels and nasal cavities were prepared for histological descriptive analyses. Results: Treatment with T and MP decreased body weight. Plasma corticosterone concentration was significantly reduced by MP treatment and presented a clear tendency to decrease after T treatment. Histological changes observed in group T included ripples, cell vacuolization, increase in the number of nuclei, and decrease in the number of cilia in the epithelial cells. Conclusion: Growth and corticosterone concentration were impaired by T and MP at the same proportion, suggesting a role of this hormone in body gain. With the exception of T, intranasal or systemic treatment with the corticosteroids evaluated in this study did not affect nasal mucosa. (Am J Rhinol Allergy 26, e46-e49, 2012; doi: 10.2500/ajra.2012.26.3702)

Changes in body water distribution during treatment with inhaled steroid in pre-school children

Primary objective: The study aimed to examine the changes in water distribution in the soft tissue during systemic steroid activity. Research design: A three-way cross-over, randomized, placebo-controlled, double-blind trial was used, including 4 weeks of fluticasone propionate pMDI 200 mug b.i.d. delivered via Babyhaler(R), budesonide pressurized metered dose inhaler (pMDI) 200 mug b.i.d. delivered via Nebuchamber(R) and placebo. Spacers were primed before use. In total, 40 children aged 1-3 years, with mild intermittent asthma were included. Twenty-five of the children completed all three treatments. At the end of each treatment period body impedance and skin ultrasonography were measured. Methods and procedures: We measured changes in water content of the soft tissues by two methods. Skin ultrasonography was used to detect small changes in dermal water content, and bioelectrical impedance was used to assess body water content and distribution. Main outcomes and results: We found an increase in skin density of the shin from fluticasone as measured by ultrasonography (p = 0.01). There was a tendency for a consistent elevation of impedance parameters from active treatments compared to placebo although overall this effect was not statistically significant (0.1< p <0.2). However, sub-analyses indicated a significant effect on whole-body and leg impedance from budesonide treatment (p <0.05). Conclusion: Decreased growth during inhaled steroid treatment seems to partly reflect generalized changes in body water.

Doubling daily inhaled corticosteroid dose is ineffective in mild to moderately severe attacks of asthma in adults

Background: Asthma guidelines recommend increasing or doubling inhaled corticosteroid (ICS) dose to treat mild and moderate exacerbations of asthma in adults. Aim: To: (i) compare the effectiveness of doubling existing daily ICS dose (fluticasone) with maintaining usual ICS dose and usual daily ICS dose accompanied by oral steroids (OS) (dexamethasone) during mild and moderately severe exacerbations of asthma in adults; (ii) examine determinants of success and failure; and (iii) compare side-effect profiles. Methods: A randomized, double-blind, placebo-controlled (double-dummy), triple crossover trial. Participants acted as their own control. Outcome measures included treatment success/failure, peak expiratory flow (PEF) after 7 days therapy or at treatment failure, and side-effects. Results: From 22 participants (nine males and 13 females), 18 pairs of data were available for maintaining usual ICS versus doubling ICS and doubling ICS versus OS, and 19 for maintaining usual ICS versus OS. Median (fifth-95th percentile) age was 46.5 (32-64) years and forced expiratory volume in one second (FEV1) 73% (29-97%) predicted. The outcome after doubling ICS was not superior to maintaining usual ICS, with 11 (61%) failures in both arms (P = 0.66). OS, with only 5 (26%) failures, was superior to maintaining usual ICS with 12 (63%) failures (P = 0.04), and to doubling ICS with 5 (28%) versus 11 (61%) failures (P = 0.07). Median PEF (as percentage of run-in best) at end-points were 90.5% (57.1-177.1) for OS, 78.3% (39.5-103.1) for maintaining usual ICS and 77.9 (27.7-110.3) for doubling ICS. Neither gender nor PEF at exacerbation were predictive of failure. Although doubling ICS was not an effective therapy overall, ICS dose at exacerbation were predictive of success in the doubling ICS arm (P = 0.04). Treatment failures when doubling daily ICS dose were more common if achieved fluticasone dose was less than 2000 mu g (three of 11, 73%) compared to 2000 mu g or greater (eight of eight, 37.5%). Increasing age and the presence of an upper respiratory tract infection (URTI) were predictive of failure with OS. Side-effects were more commonly reported with OS (52.6%) than doubling ICS (42.1%) or maintaining usual ICS (19.1%) with the most common being mood changes (36.8%), sleep disturbance (31.6%) and changes in appetite (26.3%). Conclusions: Doubling daily ICS dose per se is not effective for the treatment of mild to moderately severe exacerbations of asthma in adults. Success may depend on achieved ICS dose. Oral steroids are effective, but side-effects are common. A review of current guidelines may be warranted.

Evaluation of Dietary Laidlomycin Propionate and Synovex Plus Implants for Enhancing Performance of Feedlot Steers

One hundred fifty crossbred yearling steers with an average weight of 876 pounds were used in a 111-day experiment. Steers received either 1) no implant and no ionophore, 2) Synovex Plus¨ and no ionophore, 3) Cattlyst¨ and no implant, 4) Synovex Plus¨ and Cattlyst¨, or 5) Revalor S¨ and Rumensin¨. Implanting steers with ) Synovex Plus¨ increased gain and improved feed efficiency compared with control steers. Compared with steers not implanted, steers implanted with Synovex Plus¨ had heavier carcasses and larger ribeye areas, but similar fat thickness and yield grades. Feeding Cattlyst¨ alone did not increase gain or improve feed conversion, but there was some improvement in feedlot performance when Cattlyst¨ was fed to steers implanted with Synovex Plus¨. Steers implanted with Synovex Plus¨ and fed Cattlyst¨ had superior gains to steers implanted with Revalor S¨ and fed Rumensin¨.

Utilisation de médicaments pour le traitement de l’asthme durant la grossesse et impact sur les issues périnatales

L’asthme est l’une des pathologies chroniques les plus fréquemment rencontrées durant la grossesse, affectant environ 8% des femmes enceintes. Les lignes directrices pour le traitement de l’asthme affirment que le risque d’un développement non optimal du fœtus dû à un asthme mal maîtrisé est supérieur au risque associé à la prise de médicaments pour le traitement de l’asthme durant la grossesse. Des questions persistent par contre sur l’innocuité des hautes doses de corticostéroïdes inhalés (CSI) et très peu de données sont publiées pour les bêta2-agonistes à longue action (BALA). Un programme de recherche en deux volets a été développé afin de répondre à certaines de ces questions. Dans un premier volet, une cohorte de femmes asthmatiques accouchant au Québec de 1998 à 2008 a été assemblée à partir des bases de données de la Régie de l’assurance maladie du Québec et de MED-ÉCHO afin d’évaluer l’impact de la prise de CSI ou de BALA sur la prévalence de faible poids à la naissance (FPN), de prématurité et de bébé petit pour l’âge gestationnel (PAG). La cohorte était composée de 7376 grossesses dont 56,9% étaient exposées aux CSI et 8,8% aux BALA. Dans cette cohorte, l’utilisation de BALA n’était pas associée à des prévalences plus élevées de FPN (OR=0,81, IC95%:0,58–1,12), prématurité (OR=0,84, IC95%:0,61–1,15) ou PAG (OR=0,92, IC95%:0,70–1,20). Lors de la comparaison des BALA (salmétérol comparé au formotérol comme référence) la différence la plus importante était pour le PAG (OR=1,16, IC95%:0,67–2,02). Pour les CSI, une tendance à une augmentation de FPN, prématurité et PAG a été observée avec l’augmentation des doses. Le OR le plus élevé était pour une dose > 500 ug/jour (équivalent fluticasone) pour le FPN: (OR=1,57, IC95%:0,86–2,87). La comparaison des CSI les plus utilisés (fluticasone comparé au budésonide comme référence) montre des différences non statistiquement significatives avec la différence maximale observée pour le PAG (OR=1,10, IC95%:0,85–1,44). Dans un second volet, une sous-cohorte de femmes asthmatiques avec visites médicales pour exacerbation d’asthme au Centre hospitalier universitaire de Sherbrooke (CHUS) a été constituée pour comparer le traitement des exacerbations durant et hors grossesse. Les résultats montrent que le traitement par CS était moins fréquent et différé pour les femmes enceintes comparées aux femmes non-enceintes. Le traitement de maîtrise de l’asthme (CSI et/ou BALA) dans l’année précédant l’exacerbation était sous-optimal. Les résultats présentés dans cette thèse démontrent l’innocuité des BALA et des doses faibles à modérées de CSI pendant la grossesse pour les issues de FPN, prématurité et PAG alors que des études supplémentaires sont nécessaires afin d’évaluer l’innocuité des hautes doses de CSI. Une innocuité comparable entre les CSI (budésonide, fluticasone) et les BALA étudiés (formotérol, salmétérol) a également été démontrée. Les résultats montrent également un recours moindre aux CS pour le traitement des exacerbations d’asthme durant la grossesse comparativement à hors grossesse. Ces résultats sont un ajout important aux évidences permettant aux cliniciens et aux femmes enceintes asthmatiques de faire les meilleurs choix pour optimiser le traitement pharmacologique durant la grossesse.