Effect of Individual Patient Characteristics and Treatment Choices on Reliever Medication Use in Moderate-Severe Asthma: A Poisson Analysis of Randomised Clinical Trials.

INTRODUCTION: Even though increased use of reliever medication, including short-acting beta agonists (SABA), provides an indirect measure of symptom worsening, there have been limited efforts to assess how different patterns of reliever use correlate with symptom control and future risk of exacerbations. Here, we evaluate the effect of individual baseline characteristics on reliever use in patients with moderate-severe asthma on regular maintenance therapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR). METHODS: A drug-disease model describing the number of 24-h puffs and overnight occasions was developed with data from five clinical studies (N = 6212). The model was implemented using a nonlinear mixed effects approach and a Poisson function, considering clinical and demographic baseline characteristics. Goodness of fit and model predictive performance were assessed. Heatmaps were created to summarise the effect of concurrent baseline factors on reliever utilisation. RESULTS: The final model accurately described individual patterns of reliever use, which is significantly increased with time since diagnosis, smoking, higher Asthma Control Questionnaire (ACQ-5) score and higher body mass index (BMI) at baseline. Whilst the number of puffs decreases slowly after an initial drop relative to the start of treatment, exacerbating patients utilise significantly more reliever than those who do not exacerbate. The mean effect of FP/SAL (median dose: 250/50 µg BID) on reliever use was slightly higher than that of BUD/FOR (median dose: 160/4.5 µg BID), i.e. a 75.3% vs 69.3% reduction in reliever use, respectively. CONCLUSIONS: The availability of individual-level patient data in conjunction with a parametric approach enabled the characterisation of interindividual differences in the patterns of reliever use in patients with moderate-severe asthma. Taken together, individual demographic and clinical characteristics, as well as exacerbation history, can be considered an indicator of the degree of asthma control. High SABA reliever use suggests suboptimal clinical management of patients on maintenance therapy.

In this study, we tried to understand how patients with moderate to severe asthma use their quick-relief inhalers (like albuterol), how it relates to their symptoms and the risk of having asthma attacks. To evaluate whether differences in reliever inhaler use between patients are associated with factors like smoking or their asthma symptoms at the beginning of treatment, we gathered data from five clinical studies (n = 6212 patients). These data allowed us to create a model that predicts how often patients use their reliever inhalers (expressed as number of puffs in 24 h) during maintenance therapy with inhaled corticosteroids alone or in combination with long-acting beta agonists. The final model showed that reliever inhaler use is higher in patients who have been diagnosed with asthma for > 10 years, are smokers, have higher asthma symptom scores, and are obese or extremely obese. Patients who had asthma attacks also used their reliever inhalers more often. In addition, to understand how relief inhalers are used in real-life situations, we also created heatmaps that include a wide range of patient characteristics. By using individual patient data together with this model, we have learned that smoking, asthma control, BMI, long history of asthma and previous asthma attacks significantly influence reliever use. This information can help physicians and healthcare professionals understand know how well someone's asthma is managed. A patient who uses their reliever inhaler often is likely not to have their asthma well controlled by their regular medications.

Evaluating the affordability of asthma, chronic obstructive pulmonary disease, and cystic fibrosis medicines in a middle-income country.

BACKGROUND: A heavy financial burden is imposed on patients suffering from chronic diseases due to medicine out-of-pocket payments. OBJECTIVES: This study focuses on assessing the affordability of medications used for chronic respiratory diseases (CRDs) such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) in Iran, specifically on the category R medicines listed in the 2017 Iran drug list (IDL) that are used for the treatment of these diseases, based on the anatomical therapeutic chemical (ATC) drug code. METHODS: The affordability of medicines in mono and combination therapy approaches was assessed in CRDs using the World Health Organization/Health Action International (WHO/HAI) methodology. Accordingly, if out-of-pocket payment for 30-days of pharmacotherapy exceeds one day for the lowest-paid unskilled government worker (LPGW), it's considered non-affordable. RESULTS: Based on the monotherapy approach, our finding demonstrates that all generic medicines of category R were affordable. However, branded drugs such as Symbicort®, Pulmicort Respules®, Flusalmex®, Seretide®, Fluticort Plus®, Seroflo®, and Salmeflo® cost between 1.2 and 2.5 days' wage of LPGW and considered unaffordable despite 70% insurance coverage. Moreover, based on the affordability ratio in the combination therapy approach, all medicines used in asthma, COPD, and CF patients with mild respiratory problems are affordable except omalizumab (inj), which is non-affordable due to its high price and no insurance coverage. CONCLUSION: Results showed that the existing insurance coverage does not protect households from hardship, so more considerations are needed such as different insurance schedules and patient support programs.

Efficacy of inhaled tiotropium add-on to budesonide/formoterol in patients with bronchiolitis obliterans developing after hematopoietic stem cell transplantation.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the lung manifestation of chronic graft-versus-host disease after hematopoietic stem cell transplantation (HSCT). We assessed whether inhaled tiotropium add-on to the combination regimen including budesonide/formoterol improve pulmonary function and the chronic obstructive pulmonary disease assessment test (CAT) scores in patients with BOS. METHODS: Post-HSCT patients diagnosed as BOS in Seoul St. Mary's Hospital were reviewed retrospectively. Patients defined as BOS and treated with budesonide/formoterol/tiotropium combination therapy after budesonide/formoterol therapy from January 2011 to June 2019 were enrolled. RESULTS: Total of 86 patients were evaluated. After tiotropium add-on, the absolute FEV1 increased significantly from 1.47 ± 0.49 to 1.53 ± 0.57 L (p = 0.023) and the % predicted FEV1 from 45.0 ± 12.8 to 46.8 ± 14.5% (p = 0.031). The % predicted DLCO increased significantly after tiotropium add-on (from 61.6 ± 16.7 to 64.3 ± 16.3%, p = 0.028). Among 56 patients with complete CAT scores, no significant change was present in total CAT scores. In all, 30 of the 72 patients (41.7%) evidenced FEV1 increases > 100 mL, and 20 of 56 patients (35.7%) had CAT score decreases of ≥ 2 points. When the FEV1 and CAT scores were combined, the overall response rate to tiotropium add-on was 56.2% (41/73). The response group evidenced a significantly greater FVC increase, and a significant decrease in the RV/TLC ratio compared to the no-response group. CONCLUSIONS: Inhaled tiotropium add-on to combination budesonide/formoterol significantly improved lung function, but not respiratory symptoms, in patients with post-HSCT BOS.

Effects of treatment with montelukast alone, budesonide/formoterol alone and a combination of both in cough variant asthma.

BACKGROUND: Whether cysteinyl-leukotriene receptor antagonists (LTRAs) have a similar antitussive effect to inhaled corticosteroids and long-acting ß2-agonist (ICS/LABA), and that LTRA plus ICS/LABA is superior to LTRAs alone or ICS/LABA alone in treating cough variant asthma (CVA) remain unclear. This study aimed to investigate and compare the efficacy of montelukast alone, budesonide/formoterol alone and the combination of both in the treatment of CVA. METHODS: Ninety-nine CVA patients were assigned randomly in a 1:1:1 ratio to receive montelukast (M group: 10 mg, once daily), budesonide/formoterol (BF group: 160/4.5 µg, one puff, twice daily), or montelukast plus budesonide/formoterol (MBF group) for 8 weeks. The primary outcomes were changes in the cough visual analogue scale (VAS) score, daytime cough symptom score (CSS) and night-time CSS, and the secondary outcomes comprised changes in cough reflex sensitivity (CRS), the percentage of sputum eosinophils (sputum Eos%) and fractional exhaled nitric oxide (FeNO). CRS was presented with the lowest concentration of capsaicin that induced at least 5 coughs (C5). The repeated measure was used in data analysis. RESULTS: The median cough VAS score (median from 6.0 to 2.0 in the M group, 5.0 to 1.0 in the BF group and 6.0 to 1.0 in the MBF group, all p < 0.001), daytime CSS (all p < 0.01) and night-time CSS (all p < 0.001) decreased significantly in all three groups after treatment for 8 weeks. Meanwhile, the LogC5 and sputum Eos% improved significantly in all three groups after 8 weeks treatment (all p < 0.05). No significant differences were found in the changes of the VAS score, daytime and night-time CSSs, LogC5 and sputum Eos% among the three groups from baseline to week 8 (all p > 0.05). The BF and MBF groups also showed significant decreases in FeNO after 8 weeks treatment (p = 0.001 and p = 0.008, respectively), while no significant change was found in the M group (p = 0.457). Treatment with MBF for 8 weeks significantly improved the FEV1/FVC as well as the MMEF% pred and decreased the blood Eos% (all p < 0.05). CONCLUSIONS: Montelukast alone, budesonide/formoterol alone and a combination of both were effective in improving cough symptom, decreasing cough reflex sensitivity and alleviating eosinophilic airway inflammation in patients with CVA, and the antitussive effect and anti-eosinophilic airway inflammation were similar. Trial registration ClinicalTrials.gov, number NCT01404013.

Adherence and quality of life assessment in patients with asthma treatment with budesonide/formoterol via the Elpenhaler device: the COMPLETE study.

BACKGROUND: Asthma is a chronic inflammatory disease of the airways that causes recurring episodes of wheezing, breathlessness, chest tightness and coughing. Inhaled drugs on a daily basis are the cornerstone of asthma treatment, therefore, patient adherence is very important. METHODS: We performed a multicenter, open, non-interventional, observational, prospective study of 716 adult patients diagnosed with asthma receiving FDC (Fixed-dose combination) budesonide/formoterol via the Elpenhaler device. We assessed the adherence to treatment at 3 and 6 months (based on the MMAS-8: 8-item Morisky Medication Adherence Scale), the quality of life and change in forced expiratory volume in 1 s (FEV1) from baseline to follow-up. RESULTS: Approximately 80% of the patients showed medium to high adherence throughout the study. The mean (SD) MMAS-8 score at 6 months was 6.85 (1.54) and we observed a statistically significant shift of patients from the low adherence group to the high adherence group at 6 months. Moreover, after 6 months of treatment with FDC budesonide/formoterol, we observed an increase in the patients' quality of life that as expressed by a change 2.01 (95%CI 1.93-2.10) units in Mini AQLQ (p < 0.0001) that was more pronounced in the high adherence group. The same trend was also observed in terms of spirometry (mean FEV1 2.58 L (0.85) at the end of the study, increased by 220 mL from baseline) with a higher improvement in the medium and high adherence groups. CONCLUSIONS: Treatment with FDC of budesonide/formoterol via the Elpenhaler device was associated with improvement in asthma-related quality of life and lung function over 6 months that were more prominent in patients with higher adherence. TRIAL REGISTRATION: 2017-HAL-EL-74 (ClinicalTrials.gov Identifier: NCT03300076).

Short-Acting Beta-2-Agonist Exposure and Severe Asthma Exacerbations: SABINA Findings From Europe and North America.

BACKGROUND: Expert national/global asthma management recommendations raise the issue whether a safe threshold of short-acting beta-2 agonist (SABA) use without concomitant inhaled corticosteroids (ICS) exists. OBJECTIVE: To examine SABA and maintenance therapy associations with severe asthma exacerbations across North America and Europe. METHODS: Observational analyses of 10 SABa use IN Asthma (SABINA) datasets involving 1,033,564 patients (≥12 y) from Canada, France, the Netherlands, Poland, Spain, the United Kingdom, and the United States. Negative binomial models (incidence rate ratio [IRR] [95% CI adjusted for prespecified-covariates]) evaluated associations between SABA and exacerbations. RESULTS: Across severities, 40.2% of patients were prescribed/possessed 3 or more SABA canisters/y. Per the Global Initiative for Asthma (GINA) 2018 definitions, steps 3 to 5-treated patients prescribed/possessing 3 or more versus 1 or 2 SABAs experienced more severe exacerbations (IRR 1.08 [95% CI 1.04‒1.13], U.S. Medicare; IRR 2.11 [95% CI 1.96‒2.27], Poland). This association was not observed in all step 1 or 2-treated patients (the Netherlands, IRR 1.25 [95% CI 0.91‒1.71]; U.S. commercial, IRR 0.92 [95% CI 0.91‒0.93]; U.S. Medicare, IRR 0.74 [95% CI 0.71‒0.76]). We hypothesize that this inverse association between SABA and severe exacerbations in the U.S. datasets was attributable to the large patient population possessing fewer than 3 SABA and no maintenance therapy and receiving oral corticosteroid bursts without face-to-face health care provider encounters. In U.S. SABA monotherapy-treated patients, 3 or more SABAs were associated with more emergency/outpatient visits and hospitalizations (IRR 1.31 [95% CI 1.29‒1.34]). Most GINA 2 to 5-treated study patients (60.6%) did not have maintenance therapy for up to 50% of the time; however, the association of 3 or more SABAs and severe exacerbations persisted (IRR 1.32 [95% CI 1.18‒1.49]) after excluding these patients and the independent effect was further confirmed when U.K. SABA data were analyzed as a continuous variable in patients with up to 100% annual coverage for ICS-containing medications. CONCLUSIONS: Increasing SABA exposure is associated with severe exacerbation risk, independent of maintenance therapy. As addressed by GINA, based on studies across asthma severities where as-needed fast-acting bronchodilators with concomitant ICS decrease severe exacerbations compared with SABA, our findings highlight the importance of avoiding a rescue/reliever paradigm utilizing SABA monotherapy.

SYmbicort given as needed in mild asthma (SYGMA study): a retrospective subanalysis of the Russian population.

INTRODUCTION: While mild asthma is generally better controlled than more severe disease, patients with mild asthma may experience severe exacerbations. Definite differences between countries in terms of asthma severity and control were described previously. Since SYGMA was a global study, this sub-analysis was conducted in geographic region to investigate potential regional specificities. METHODS: The SYGMA2 trial is double-blind multicenter study involving patients ≥12 years of age with mild asthma (n = 4176), eligible for regular treatment with inhaled corticosteroid (ICS). We conducted an open-label descriptive subanalysis of the baseline characteristics of the Russian population (n = 579) comparing to rest of participants of SYGMA2 trial from other 24 countries. The subanalysis is solely descriptive and will be used for hypothesis generation. RESULTS: The Russian population of patients with mild asthma hardly differs from the population in other countries in terms of baseline demographic and anthropometric characteristics, smoking status, and duration of asthma. At the study entry few patients from Russia received maintenance therapy with ICS and had symptom control, but the majority was uncontrolled on short-acting bronchodilators, thus the uncontrolled/controlled ratio was 52%/48% vs 45%/55% in other countries. More patients with mild asthma in the Russian group had faced at least one severe exacerbation in the previous year (30.1% vs 20.7%). CONCLUSIONS: The subanalysis revealed a delayed prescription of controller (ICS) therapy and overuse of short-acting bronchodilators in the Russian population with mild asthma. These factors can lead to insufficient symptom control and higher risk of severe exacerbation in the Russian population with mild asthma.

A delayed diagnosis of atypical immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome: A case report.

INTRODUCTION: Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome is a rare monogenic autoimmune disease, which is caused by mutations in the forkhead box protein 3 gene, can affect various systems. The typical clinical manifestations of IPEX are enteropathy, type 1 diabetes mellitus, and skin diseases. However, some atypical phenotypes can easily be misdiagnosed clinically. PATIENT CONCERNS: A 9-year-and-7-month old patient suffered from recurrent wheezing, hematochezia, and eczematous dermatitis at the age of six months, but did not have any manifestations of autoimmune endocrinopathy. The patient was treated with glucocorticoids for more than six years, and he developed bronchiectasis. DIAGNOSIS: Whole exome sequencing revealed a hemizygous pathogenic mutation c.1010G>A, p. (Arg337Gln) in Forkhead box protein 3 gene (NM_014009.3). INTERVENTIONS: The patient was treated with oral mycophenolate mofetil combined with inhaled budesonide formoterol for six months after diagnosis. OUTCOMES: The respiratory symptoms of the patient seemed to be controlled but eczematous dermatitis progressed, which led the patient to give up the treatment. CONCLUSION: Early diagnosis and treatment of IPEX are crucial. Lung injury may be a major problem in the later stages of atypical IPEX, and mycophenolate mofetil seems to control the respiratory symptoms, but could induce significant skin side effects.

Assessment of Adherence and Asthma Medication Ratio for a Once-Daily and Twice-Daily Inhaled Corticosteroid/Long-Acting ß-Agonist for Asthma.

BACKGROUND: Although efficacy and safety of fluticasone furoate/vilanterol (FF/VI) and budesonide/formoterol (BUD/F) have been demonstrated in clinical studies, real-world comparisons of utilization have not been performed. OBJECTIVE: To compare similar patients with asthma initiating FF/VI or BUD/F on measures of adherence, persistence, and the asthma medication ratio (AMR). METHODS: This was a retrospective cohort study of commercial and Medicare Advantage with Part D enrollees initiating FF/VI or BUD/F for asthma. Adult patients (≥18 years) with at least 15-month (12-month preindex and 3-month postindex) continuous enrollment and 1 or more asthma diagnosis code were eligible for the study. Patients with a history of fixed-dose inhaled corticosteroid/long-acting ß-agonist and other respiratory disorders (chronic obstructive pulmonary disease, cystic fibrosis, acute respiratory failure) in the baseline period were excluded. Propensity-score matching was used to balance cohorts on baseline characteristics. Logistic regression and Cox-proportional hazard models were used to assess differences. RESULTS: A total of 9951 patients met all criteria. After propensity-score matching, 1725 patients were matched in each cohort. Subjects who initiated FF/VI had a significantly higher mean proportion of days covered (P < .001), had 86% greater odds of having a proportion of days covered value of greater than or equal to 0.80 (adjusted odds ratio, 1.86; 95% CI, 1.51-2.30), 26% lower risk of discontinuation (adjusted hazard ratio, 0.74; 95% CI, 0.69-0.79), and 36% greater odds of an AMR of greater than or equal to 0.50 (adjusted odds ratio, 1.36; 95% CI, 1.23-1.50) compared with BUD/F. CONCLUSIONS: Adherence and treatment persistence were low in both cohorts; however, patients initiating once-daily FF/VI were more likely to be adherent, have an AMR of greater than or equal to 0.5, and were less likely to discontinue therapy compared with patients initiating twice-daily BUD/F (GlaxoSmithKline Study HO1617302/206482).

Airway pathology in severe asthma is related to airflow obstruction but not symptom control.

BACKGROUND: Patients with asthma present structural and inflammatory alterations that are believed to play a role in disease severity. However, airway remodeling and inflammation have not been extensively investigated in relation to both symptom control and airflow obstruction in severe asthmatics. We aimed to investigate several inflammatory and structural pathological features in bronchial biopsies of severe asthmatics that could be related to symptom control and airflow obstruction after standardized treatment. METHODS: Fifty severe asthmatics received prednisone 40 mg/d for 2 weeks and maintenance therapy with budesonide/formoterol 400/12 µg twice daily + budesonide/formoterol 200/6 µg as needed for 12 weeks. Endobronchial biopsies were performed at the end of 12 weeks. We performed extensive immunopathological analyses of airway tissue inflammation and remodeling features in patients stratified by asthma symptom control and by airflow obstruction. RESULTS: Airway tissue inflammation and remodeling were not associated with symptom control. Asthmatics with persistent airflow obstruction had greater airway smooth muscle (Asm) area with decreased periostin and transforming growth factor beta-positive cells within Asm bundles, in addition to lower numbers of chymase-positive mast cells in the submucosa compared to patients with nonpersistent obstruction. CONCLUSIONS: Symptom control in severe asthmatics was not associated with airway tissue inflammation and remodeling, although persistent airflow obstruction in these patients was associated with bronchial inflammation and airway structural changes.

Metabolic changes of different high-resolution computed tomography phenotypes of COPD after budesonide-formoterol treatment.

BACKGROUND: Metabolomics is the global unbiased analysis of all the small-molecule metabolites within a biological system. Metabolic profiling of different high-resolution computed tomography (HRCT) phenotypes of COPD patients before and after treatment may identify discriminatory metabolites that can serve as biomarkers and therapeutic agents. PATIENTS AND METHODS: 1H nuclear magnetic resonance spectroscopy (1H-NMR)-based metabolomics was performed on a discovery set of plasma samples from 50 patients with stable COPD. Patients were assigned into two groups on the basis of HRCT findings including phenotype E (n=22) and phenotype M (n=28). After budesonide-formoterol treatment (160/4.5 µg ×2 inhalations twice daily for 3 months), clinical characteristics and metabolites were then compared between phenotype E pretreatment and posttreatment, phenotype M pretreatment and posttreatment, phenotype E pretreatment and phenotype M pretreatment, and phenotype E posttreatment and phenotype M posttreatment. RESULTS: Inhaled budesonide-formoterol therapy for both phenotype E (emphysema without bronchial wall thickening) and phenotype M (emphysema with bronchial wall thickening) was effective. However, phenotype E and phenotype M were different in response to therapy. Patients with phenotype M in response to therapeutic effects were significantly greater compared with phenotype E. Certain metabolites were identified, which were closely related to the treatment and phenotype. Metabolic changes in phenotype E or phenotype M after treatment may be involved with adenosine diphosphate (ADP), guanosine, choline, malonate, tyrosine, glycine, proline, l-alanine, l-valine, l-threonine leucine, uridine, pyruvic acid, acetone and metabolism disturbance. Metabolic differences between phenotype E and phenotype M in pretreatment and posttreatment covered glycine, d-glucose, pyruvic acid, succinate, lactate, proline, l-valine and leucine. CONCLUSION: Bronchial wall thickening in COPD may be an indicator for predicting the better response to the treatment with bronchodilator and corticosteroid. The identification of metabolic alterations provides new insights into different HRCT phenotypes and therapeutic assessment of COPD.

Routine Use of Budesonide/Formoterol Fixed Dose Combination in Elderly Asthmatic Patients: Practical Considerations.

Asthma has been demonstrated to be as common in the elderly as in younger age groups. Although no specific recommendations exist to manage the disease differently in older individuals, functional features and clinical presentations may be affected by age per se, and by age-related conditions, such as comorbidities and polypharmacy. In this review article, we aimed to explore the efficacy and safety in elderly asthmatic patients of one of the most currently used inhaled treatments for asthma, that is, the fixed-dose combination of budesonide/formoterol. We attempted to address some practical questions that are relevant to the daily practice of clinicians. We focused on the efficacy and real-world effectiveness of inhaled corticosteroids and long-acting ß-adrenergic bronchodilators (ICS/LABA) as treatment in the elderly population, since data are extrapolated from younger populations. We investigated whether a maintenance and reliever therapy approach is more effective in the elderly as opposed to maintenance regimens, from both the general practitioner's and the pulmonologist's perspective. To address these questions, we scanned electronic databases (PubMed, MEDLINE, Embase, Scopus and Google Scholar) from the date of inception up to October 2016 with a cross-search using the following keywords: 'asthma', 'elderly', 'SMART therapy', 'MART therapy', 'Turbuhaler', and 'budesonide/formoterol'. The available literature on the topic confirms that when the age-associated changes are properly managed in clinical practice, asthma in older populations can be optimally controlled with inhaled treatment including ICS/LABA. This also applies for the budesonide/formoterol fixed combination, thus allowing for the maintenance and reliever therapy approach.

Can computed tomography and carbon monoxide transfer coefficient diagnose an asthma-like phenotype in COPD?

BACKGROUND AND OBJECTIVE: Post-mortem and computed tomography (CT) studies indicated that emphysema is a feature of COPD even in the 'blue bloater/chronic bronchitis' type. We aim to test the hypothesis that the non-emphysematous patients are distinct from the main body of COPD and are more akin to asthmatic patients. METHODS: We studied 54 patients with COPD. Emphysema was measured by Goddard's visual scoring of CT scan and the carbon monoxide transfer coefficient (KCO). Bronchial biopsy was offered for thickness of basement membrane (BM) (≥7 µm) as a marker of remodelling in irreversible asthma. Spirometry was repeated after therapy with Budesonide/Formoterol for 1 year. RESULTS: The non-emphysematous phenotype were 24 of 54 patients (44%) by CT scan and 23 of 54 patients (43%) by KCO, showing agreement in 53 out of 54 patients. The non-emphysematous patients were younger, had higher forced expiratory volume in 1 s (FEV1 ) (median 61% vs 49.7%), greater prevalence of hypertrophy of nasal turbinates and higher serum IgE. The emphysematous phenotype had lower BMI and greater dyspnoea score. The BM was thickened in 11 of 14 and 0 of 10 patients in the non-emphysematous and emphysematous groups, respectively. Three patients without emphysema and a normal BM normalized their FEV1 upon receiving inhaled corticosteroid (ICS)/long-acting ß2 agonist (LABA). All the non-emphysematous improved their FEV1 after ICS/LABA (median = 215 mL). The median decline in the emphysematous was -65 mL. CONCLUSION: The non-emphysematous phenotype of COPD displays important features of asthma: clinical picture, histology and response to ICS. CT and KCO can predict spirometric response to ICS/LABA.

Therapeutic effect of budesonide/formoterol, montelukast and N-acetylcysteine for bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) is currently treated with systemic corticosteroids despite poor efficacy and side effects. This study investigated the therapeutic effect of budesonide/formoterol, montelukast and n-acetylcysteine, which are suggested as treatment options for BOS after HSCT. METHODS: After diagnosis of BOS, 61 patients were treated with budesonide/formoterol, montelukast and n-acetylcysteine for 3 months. Pulmonary function test and COPD assessment test (CAT) were performed before and after the combination therapy. Therapeutic response was evaluated by changes in forced expiratory volume in 1 s (FEV1) or CAT score. RESULTS: After 3 months of combination treatment, mean FEV1 increased by 220 mL (p < 0.001) and residual volume decreased by 200 mL (p =0 .005). Median CAT score also significantly decreased from 15.5 to 11.0 (p = 0.001). The overall response rate to combination therapy was 82 %. Comparing the no-response group and the response group, the forced vital capacity (% predicted) decline between pre-HSCT and BOS diagnosis was significantly greater in the response group (p = 0.036). CONCLUSION: Combination treatment with budesonide/formoterol, montelukast and n-acetylcysteine significantly improved lung function and respiratory symptoms in patients with BOS after allogeneic HSCT without serious side effects.

Associação de budesonida 200 mcg/formoterol 6 mcg para asma / Association of budesonide 200 mcg / formoterol 6 mcg for asthma

CONTEXTO: A asma é uma doença inflamatória crônica das vias aéreas associada à hiperresponsividade das vias aéreas, que leva a episódios recorrentes de sibilos, dispneia, opressão torácica e tosse. Estima-se que existam 20 milhões de asmáticos no Brasil, considerando-se uma prevalência global de 10%. No Protocolo Clínico e Diretrizes Terapêuticas da Asma do Ministério da Saúde (2013), as condutas medicamentosas para tratamento inicial da asma são feitas de acordo com a gravidade da doença e o tratamento de manutenção é baseado no grau de controle. Entre as várias opções terapêuticas para o tratamento de manutenção da asma, o PCDT relaciona associação de dose fixa de formoterol mais budesonida: cápsula ou pó inalante de 12 mcg/400 mcg e de 6mcg/200mcg, já disponíveis no SUS. EVIDÊNCIAS CIENTÍFICAS: Os resultados apresentados pelos ensaios clínicos randomizados Morice AH et. al, 2007 e Morice AH et. al, 2008 sugerem que a associação budesonida e formoterol em aerossol é eficaz e segura no tratamento da asma brônquica, no entanto, não demonstra superioridade clínica em relação à formulação em pó seco do mesmo medicamento, que já está disponível no SUS atualmente. Não houve diferenças clinicamente importantes entre as apresentações com relação aos eventos adversos, sinais vitais e parâmetros laboratoriais. CONSIDERAÇÕES FINAIS: A evidência atualmente disponível sobre eficácia e segurança da formulação que associa budesonida e formoterol em aerossol para tratamento da asma é baseada em ensaios clínicos randomizados. DELIBERAÇÃO FINAL: A associação de budesonida 200mcg/ formoterol 6mcg aerossol é eficaz e segura no tratamento da asma brônquica, no entanto, não demonstra superioridade clínica em relação à formulação em pó seco, já disponível no SUS. Não foram apresentadas novas evidências clínicas na consulta pública e o novo preço proposto pela empresa não alterou a primeira avaliação, que observou que o preço proposto é maior que a alternativa terapêutica já incorporada. Assim, as informações prestadas demonstraram que este medicamento não é melhor nem pior do que os demais, apresentando preço mais alto e, assim, não traria grande benefício de se incluir no SUS. Após a avaliação das contribuições realizadas na consulta pública, os membros presentes na 32ª Reunião da CONITEC deliberaram por não recomendar a incorporação da associação de budesonida 200mcg/ formoterol 6mcg em suspensão aerossol para o tratamento da asma. Foi assinado o Registro de Deliberação nº 106/2015. DECISÃO: PORTARIA Nº 13, de 9 de abril de 2015 - Torna pública a decisão de não incorporar a associação de budesonida 200mcg/ formoterol 6mcg em suspensão aerossol para o tratamento da asma no âmbito do Sistema Único de Saúde - SUS.