COPD patients prescribed inhaled corticosteroid in general practice: Based on disease characteristics according to guidelines?

In a primary care setting, our aim was to investigate characteristics of patients classified as having chronic obstructive pulmonary disease (COPD) and currently being prescribed inhaled corticosteroids (ICSs). The electronic patient record system in each participating general practice was searched for patients coded as COPD (ICPC, Second Edition code R95) and treated with ICS (ACT code R03AK and R03BA, that is, ICS in combination with a long-acting ß2-agonist) or ICS as monotherapy. Data, if available, on demographics, smoking habits, spirometry, COPD medication, symptom score, blood eosinophils, co-morbidity and exacerbation history were retrieved from the medical records for all identified cases. Of all patients registered in the 138 participating general practices, 12.560 (3%) were coded as COPD, of whom 32% were prescribed ICS. The final study sample comprised 2.289 COPD patients currently prescribed ICS (98% also prescribed long-acting ß2-agonist), with 24% being coded as both COPD and asthma. Post-bronchodilator spirometry was available in 79% (mean forced expiratory volume in 1 second 60% pred (standard deviation (SD) 23.3)), symptom severity score in 53% (mean Medical Research Council score 2.7 (SD 1.1)) and 56% of the COPD patients had had no exacerbation in the previous year (and 45% not within the 2 previous years). Blood eosinophils were measured in 67% of the patients. Information on severity of airflow limitation was missing in 15% of the patients, and the combined information on symptom severity and exacerbation history was missing in in 46%. Most of the patients (74%) were managed only by their general practitioner. Although only one-third of the COPD patients were prescribed ICSs, our findings from this study of a large cohort of patients prescribed ICSs for COPD in general practice suggest that more detailed assessment of diagnosis and disease characteristics is likely to improve the risk-benefit ratio of maintenance therapy with ICSs in COPD patients managed in primary care.

Therapy for Pulmonary Arterial Hypertension in Adults: Update of the CHEST Guideline and Expert Panel Report.

BACKGROUND: Pulmonary arterial hypertension (PAH) carries a poor prognosis if not promptly diagnosed and appropriately treated. The development and approval of 14 medications over the last several decades have led to a rapidly evolving approach to therapy, and have necessitated periodic updating of evidence-based treatment guidelines. This guideline statement, which now includes a visual algorithm to enhance its clinical utility, represents the fourth iteration of the American College of Chest Physicians Guideline and Expert Panel Report on Pharmacotherapy for PAH. METHODS: The guideline panel conducted an updated systematic review to identify studies published after those included in the 2014 guideline. A systematic literature search was conducted using MEDLINE via PubMed and the Cochrane Library. The quality of the body of evidence was assessed for each critical or important outcome of interest using the Grading of Recommendations Assessment, Development and Evaluation approach. Graded recommendations and ungraded consensus-based statements were developed and voted on using a modified Delphi technique to achieve consensus. RESULTS: Two new recommendations on combination therapy and two ungraded consensus-based statements on palliative care were developed. An evidence-based and consensus-driven treatment algorithm was created to guide the clinician through an organized approach to management, and to direct readers to the appropriate area of the document for more detailed information. CONCLUSIONS: Therapeutic options for the patient with PAH continue to expand through basic discovery, translational science, and clinical trials. Optimal use of new treatment options requires prompt evaluation at an expert center, utilization of current evidence-based guidelines, and collaborative care using sound clinical judgment.

Comparative efficacy of inhaled medications (ICS/LABA, LAMA, LAMA/LABA and SAMA) for COPD: a systematic review and network meta-analysis.

PURPOSE: To assess the comparative efficacy of short-acting muscarinic antagonists (SAMAs), long-acting muscarinic antagonists (LAMAs), LAMA in combination with long-acting beta-agonists (LABAs; LAMA/LABAs) and inhaled corticosteroids (ICS) in combination with LABA (ICS/LABAs) for the maintenance treatment of COPD. MATERIALS AND METHODS: We systematically reviewed 74 randomized controlled trials (74,832 participants) published up to 15 November 2017, which compared any of the interventions (SAMA [ipratropium], LAMA [aclidinium, glycopyrronium, tiotropium, umeclidinium], LAMA/LABA [aclidinium/formoterol, indacaterol/glycopyrronium, tiotropium/olodaterol, umeclidinium/vilanterol] and ICS/LABA [fluticasone/vilanterol, budesonide/formoterol, salmeterol/fluticasone]) with each other or with placebo. A random-effects network meta-analysis combining direct and indirect evidence was conducted to examine the change from baseline in trough FEV1, transition dyspnea index, St George's Respiratory Questionnaire and frequency of adverse events at weeks 12 and 24. RESULTS: Inconsistency models were not statistically significant for all outcomes. LAMAs, LAMA/LABAs and ICS/LABAs led to a significantly greater improvement in trough FEV1 compared with placebo and SAMA monotherapy at weeks 12 and 24. All LAMA/LABAs, except aclidinium/formoterol, were statistically significantly better than LAMA monotherapy and ICS/LABAs in improving trough FEV1. Among the LAMAs, umeclidinium showed statistically significant improvement in trough FEV1 at week 12 compared to tiotropium and glycopyrronium, but the results were not clinically significant. LAMA/LABAs had the highest probabilities of being ranked the best agents in FEV1 improvement. Similar trends were observed for the transition dyspnea index and St George's Respiratory Questionnaire outcomes. There were no significant differences in the incidences of adverse events among all treatment options. CONCLUSION: LAMA/LABA showed the greatest improvement in trough FEV1 at weeks 12 and 24 compared with the other inhaled drug classes, while SAMA showed the least improvement. There were no significant differences among the LAMAs and LAMA/LABAs within their respective classes.

Evaluation of changes in guidelines for medication management of stable chronic obstructive pulmonary disease.

RATIONALE, AIMS AND OBJECTIVES: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines are well-known international clinical practice guidelines for chronic obstructive pulmonary disease (COPD). The objective of this study was to examine how treatment recommendations and the quality of supporting evidence for pharmacologic management of stable COPD have evolved since the initial guidance issued in 2001. METHODS: Recommendations in the 2001 and 2011 GOLD guidelines, along with the evidence grades (i.e. A, B, C, D), were identified and abstracted. We determined the distribution and evolution of recommendations across levels of evidence and treatment categories over time. RESULTS: There were 35 and 54 recommendations identified in the 2001 and 2011 guidelines, respectively. Twenty-six recommendations were common to the 2001 and 2011 guidelines, with eight having the same evidence grade in both versions and three having a grade change (one upgraded and two downgraded). Twenty-eight new recommendations were added in 2011. Bronchodilators, glucocorticosteroids, and phosphodiesterase-4 inhibitors are the classes of pharmacologic treatment with the most prominent changes regarding emerging evidence and the number of recommendations. Approximately 45% of the graded recommendations were supported by well-designed randomized controlled trials, i.e. grade A. CONCLUSIONS: The GOLD guideline recommendations have changed considerably over the past 11 years, which reflects a dynamic evidence base and perhaps a change in the way guideline developers view the evidence to inform recommendations. Given the large number of recommendations with lower grade levels, there continues to be substantial opportunity to inform gaps in the evidence base with high-quality studies.

Current and future therapies for airway mucus hypersecretion.

Mucus hypersecretion is a prominent feature of chronic inflammatory diseases of the airways, including asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis, but little is known about the effects of current therapies for airway disease because of the difficulties in quantifying mucus hypersecretion in clinical studies. Anticholinergics may reduce mucus hypersecretion, whereas beta2 agonists and mucolytics have little obvious effect. Corticosteroids are highly effective in inhibiting mucus hypersecretion in asthma by suppressing the underlying inflammatory process, but are ineffective in COPD and cystic fibrosis. Novel approaches in the future may include inhibition of sensory neuropeptides by tachykinin antagonists, modulators of sensory nerves or K+ channel openers. Inhibition of Th2 cytokines (interleukin [IL]4, IL9, IL13) may also be effective in asthma. In COPD inhibition of neutrophil-derived proteases by small molecule inhibitors or inhibiting neutrophilic inflammation in the airways by reducing neutrophil chemotaxis may also be effective strategies. Several novel targets involved in mucus hypersecretion have recently been identified, including epidermal growth factor receptors, MARCKs, Ca2+-activated Cl- channels and mitogen-activated protein kinases. However, the clinical benefits from inhibiting mucus hypersecretion are still not certain, casting some doubts on this therapeutic approach.

Classification of cilio-inhibiting effects of nasal drugs.

OBJECTIVE/HYPOTHESIS: Nasal drug formulations are widely used for a local therapeutic effect, but are also used for systemic drug delivery. In the development of new nasal drugs, the toxic effects on the mucociliary clearance and therefore on the ciliated tissue is of importance. In this study, the effect of nasal drugs and their excipients on the ciliary beat frequency (CBF) is investigated. STUDY DESIGN: Experimental, in vitro. METHODS: CBF is measured by a photograph-electric registration method. Excised ciliated chicken trachea tissue is incubated for 15 minutes in the formulation, followed by a reversibility test. To estimate the ciliostatic potential, a classification is given of all tested formulations. According to the CBF, after 60 minutes every drug or excipient could be classified as follows: cilio-friendly: after 60 minutes the CBF has regained 75% or more of its initial frequency; cilio-inhibiting: after 60 minutes the CBF has regained between 25% and 75% of its initial frequency; or ciliostatic: after 60 minutes the CBF has regained 25% or less of its initial frequency. RESULTS: Most formulations used are cilio-friendly or cilio-inhibiting. Only some are ciliostatic. Preservatives have a major role in the cilio-inhibiting effect of the drug. Also, other additives can contribute to the toxicity profile of nasal drug formulations. CONCLUSION: This classification of the cilio-inhibiting potential of nasal drug formulations is a valuable tool in the design of safe nasal drugs. The number of animal studies in vivo can be reduced substantially by using this in vitro screening technique. This study demonstrates that the effect on ciliary movement of most drug formulations is due to the preservatives and/or additives and mostly not to the drug itself.

Intolerancia a antiinflamatorios no esteroideos con reacción respiratoria: aspectos clínicos y diagnósticos / Intolerance to non-steroidal anti-inflammatory drugs with respiratory reaction: clinical and diagnostic features

Fundamento: La prevalencia de la intolerancia a antiinflamatorios no esteroideo (AJ­NEs) es en adultos con asma del LO al 30%. El mecanismo e desconocido aunque se cree que e debe a una inhibición de la ciclooxigenasa con aumento de los leucotrie-nos. Clínicamente se caracteriza por rinoconjuntivitis y asma. El diagnóstico de sospecha se basa en la historia clínica y el definitivo, en el test de provocación oral (TPO). El objetivo del presente estudio es analizar los diferentes aspecto relacionado con el diagnóstico de la intolerancia a AINEs (lA) en pacientes que presentaron clínica respiratoria tras la ingesta de un AINE, y comparar los datos recogido en la historia clínica con los resultados obtenidos con un protocolo de estudio. Métodos: Se ha estudiado a 150 pacientes con sospecha de intolerancia a AINEs con reacción respiratoria. El TPO se consideró positivo cuando el descenso del pico de flujo fue 2:15% respecto al basal y/o aparecían síntomas nasooculares y/o bronquiales. El diagnóstico se estableció por anarnnesis si el cuadro clínico era considerado grave, o por TPO cuando dos AINEs di tintos estructuralmente provocaban idéntica reacción. La intolerancia a AINEs se descartó cuando e toleró 1 g de ácido acetil alicílico (AAS). A un subgrupo de 20 pacientes diagnosticados de intolerancia a AINEs se les realizó una provocación con paracetamol para comprobar su tolerancia. Resultados: El 32% se diagnosticó de intolerancia a AJNEs (el 74% por protocolo de estudio y el resto, por historia clínica). Los fármaco responsables de las reaccione fueron: AAS (95%), pirazolonas (36%), arilpropiónicos (10%). oxicam (2%), fenamato (2%) y paracetamol (2%). Con el TPO se observó: rinitis (9%), asma (12%) rinitis con de censo del pico de flujo de entre el 15 y el 25o/c (7%) y rinoconjuntiviti y asma (72%). Se detectó una asociación estadísticamente significativa (x2) entre lo dato de la historia clínica y el TPO (p<Ü.05). El 40% de los pacientes intolerantes tuvieron una reacción positiva con el paracetamol. el 25% con dosis superiores a l g. Conclusiones: La significativa reproductibilidad entre los datos de la historia clínica y el TPO confirma la necesidad de valorar cada caso individualmente, con el fin de utilizar las pruebas diagnósticas que menor riesgo conlleve para el paciente (AU)

Background: In adult asthma. non­steroidal anti­inflammatory drug ( SAID) prevalence is about 10­30%. The causative mechanism is thought to be due to cyclooxigenase inhibition, which cause an increase of leukotrienes. Clinical finding are rhinoconjuctivitis and a thma. Diagnosis is based on clínical history and oral challenge tests (OCT). To analize different features in the diagnosis of SAIDs intolerance in patient with respiratory symptoms after NSAID ingestion and to compare data from clínica] history with our protocols results. Methods: One hundred and fifty patients uspected of respiratory reaction by ( SAIDs) were studied. OCT wa positive if PEFR fell >?5% from the basal values with bronchial symptoms and/or nasoocular symptoms appeared. Diagnosis was establi hed by clinical history if the clinical features are considered hazard for patients life or by OCT when two structurally different SA!Ds caused the same reaction. Intolerance was ruled out if patient tolerated up to 1 g of ASA. 20 patients diagnosed of lA were challenged with paracetamol up to 2 g in order to establih the tolerance to this SAID. Results: Thirty­two percent patient were intolerant: 74% based on study protocol. Causative drugs were: ASA (95%). yrazole (36% ). Aril propionics ( 10%), Oxicam (2~ ), Fenamics (2%), and paracetamol (2%). Along OCTs. rhinitis was een in 9%. asthma in 12%. rhinitis with PEFR fall of about 15­25% in 7% and rhinoconjuntivitis and asthma in 72%. A statistical association (X2) between clínica! finding and OCTs (p<0.05) was found. Forty percent of intolerant patients suffered a positive reaction with paracetamol. Twenty­five percent with do es > 1 g. Conclusions: The significant reproducibility between data from clínical history and OCT confirm that it is necesary to value each ca e individually for using diagnostic test with low risk for patients (AU)