Reliever Medication Use Research Articles

A Simulation Study of the Effect of Clinical Characteristics and Treatment Choice on Reliever Medication Use, Symptom Control and Exacerbation Risk in Moderate-Severe Asthma.

The relationship between immediate symptom control, reliever medication use and exacerbation risk on treatment response and factors that modify it have not been assessed in an integrated manner. Here we apply simulation scenarios to evaluate the effect of individual baseline characteristics on treatment response in patients with moderate-severe asthma on regular maintenance dosing monotherapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR). Reduction in reliever medication use (puffs/24h), change in symptom control scores (ACQ-5), and annualised exacerbation rate over 12months were simulated in a cohort of patients with different baseline characteristics (e.g. time since diagnosis, asthma control questionnaire (ACQ-5) symptom score, smoking status, body mass index (BMI) and sex) using drug-disease models derived from large phaseIII/IV clinical studies. Simulation scenarios show that being a smoker, having higher baseline ACQ-5 and BMI, and long asthma history is associated with increased reliever medication use (p < 0.01). This increase correlates with a higher exacerbation risk and higher ACQ-5 scores over the course of treatment, irrespective of the underlying maintenance therapy. Switching non-responders to ICS monotherapy to combination therapy after 3months resulted in immediate reduction in reliever medication use (i.e. 1.3 vs. 1.0 puffs/24h for FP/SAL and BUD/FOR, respectively). In addition, switching patients with ACQ-5 > 1.5 at baseline to FP/SAL resulted in 34% less exacerbations than those receiving regular dosing BUD/FOR (p < 0.01). We have identified baseline characteristics of patients with moderate to severe asthma that are associated with greater reliever medication use, poor symptom control and higher exacerbation risk. Moreover, the effects of different inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) combinations vary significantly when considering long-term treatment performance. These factors should be considered in clinical practice as a basis for personalised management of patients with moderate-severe asthma symptoms.

AM-301, a barrier-forming nasal spray, versus saline spray in seasonal allergic rhinitis: A randomized clinical trial.

Saline nasal sprays are frequently used in the management of seasonal allergic rhinitis (SAR) for the cleansing and clearing of aeroallergens from the nasal cavity. Also using a drug-free approach, AM-301 nasal spray is forming a thin film barrier on the nasal mucosa to prevent contact with allergens, trap them, and facilitate their discharge. A clinical trial compared the efficacy, safety, and tolerability of AM-301 and saline spray in SAR. A total of 100 patients were randomized 1:1 to self-administer AM-301 or saline 3 × daily for 2 weeks. Primary efficacy endpoint: reduction in mean daily reflective Total Nasal Symptom Score (rTNSS). Secondary efficacy endpoints: reduction in mean instantaneous TNSS and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), global impression of efficacy. Safety and tolerability: adverse events, relief medication use, symptom-free days, global impression of tolerability. AM-301-treated patients achieved a significantly lower rTNSS than the saline group (LS square means difference -1.1, 95% CI -1.959 to -0.241, p = .013) with improvement observed across all individual nasal symptoms. Likewise, all secondary endpoints showed statistical significance in favor of AM-301; for example, quality of life was significantly improved overall (p < .001) as well as for each individual RQLQ domain. Both treatments showed similarly good safety and tolerability. With AM-301, fewer patients used relief medication and more enjoyed symptom-free days compared to saline treatment. AM-301 was more effective than saline in improving SAR nasal symptoms and related quality of life while offering similar tolerability, demonstrating the benefits of a barrier approach.

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

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). 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. 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: 250/50μg BID) on reliever use was slightly higher than that of BUD/FOR (median dose: 160/4.5μg BID), i.e. a 75.3% vs 69.3% reduction in reliever use, respectively. 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.

The Relationship Between Pediatric Attention-Deficit/Hyperactivity Disorder Symptoms and Asthma Management

PurposeChildren with comorbid Attention-Deficit/Hyperactivity Disorder (ADHD) and asthma are at an increased risk for adverse health outcomes and reduced quality of life. The objective of these analyses was to examine if self-reported ADHD symptoms in children with asthma are associated with asthma control, asthma controller medication adherence, quick relief medication use, pulmonary function, and acute healthcare utilization. MethodsWe analyzed data from a larger study testing a behavioral intervention for Black and Latinx children with asthma aged 10–17 years and their caregivers. Participants completed the Conners-3AI self-report assessment for ADHD symptoms. Asthma medication usage data were collected for 3 weeks following baseline via electronic devices fitted to participants' asthma medications. Other outcome measures included the Asthma Control Test, self-reported healthcare utilization, and pulmonary function measured by spirometry testing. ResultsThe study sample consisted of 302 pediatric participants with an average age of 12.8 years. Increased ADHD symptoms were directly associated with reduced adherence to controller medications, but no evidence of mediation was observed. Direct effects of ADHD symptoms on quick-relief medication use, health care utilization, asthma control, or pulmonary function were not observed. However, the effect of ADHD symptoms on emergency room visits was mediated by controller medication adherence. DiscussionADHD symptoms were associated with significantly reduced asthma controller medication adherence and indirectly with emergency room visits. There are significant potential clinical implications to these findings, including the need for the development of interventions for pediatric asthma patients with ADHD.

Lockdown Fatigue in Pediatric Respiratory Patients: Lessons from the First COVID-19 Year.

Lockdown policies have been implemented worldwide to limit the spread of COVID-19. "Lockdown fatigue" is a state of exhaustion related to the accumulating effects of repeated lockdowns. The aim of the current study was to examine the effects of repeated lockdowns on children with respiratory disorders. Data on children aged 0-18 years old with respiratory disorders were collected by an electronic survey during the third lockdown in Israel. The retrieved information included demographics and baseline medical status, respiratory clinical status during the third lockdown compared to pre-lockdown periods, lockdown adherence, lifestyle modifications and caregiver emotional status. The results were compared to those of a similar questionnaire distributed during the first lockdown. A total of 234 patients (62% males, 37% females, mean age 6.8 years (confidence interval 6.1-7.5)) were enrolled. Respiratory symptoms and exacerbation frequency were reduced in 76 (35.5%) and 58 (27.4%) patients, respectively, compared to the pre-lockdown period and similar to the first lockdown (p = 0.840 and p = 0.063, respectively). However, compared to the first lockdown, the third lockdown was associated with greater use of reliever medications (p = 0.006), less use of inhaled corticosteroids as routine treatment (p = 0.027), and more pediatric emergency room visits and hospitalizations (p = 0.001 and p &lt; 0.001, respectively). The results also showed an increase in sedentary lifestyle (e.g., reduced physical activity (p = 0.025), less healthy eating habits (p = 0.001)) and reduced adherence to lockdown policies (p &lt; 0.001). These data show that the continuing stability of clinical improvement during lockdown was accompanied by deleterious sequelae that potentially indicate "lockdown fatigue" among children with respiratory disorders.

An Algorithm for Strategic Continuation or Restriction of Asthma Medication Prior to Exercise Challenge Testing in Childhood Exercise Induced Bronchoconstriction.

Exercise induced bronchial (EIB) constriction is a common and highly specific feature of pediatric asthma and should be diagnosed with an exercise challenge test (ECT). The impact of EIB in asthmatic children's daily lives is immense, considering the effects on both physical and psychosocial development. Monitoring childhood asthma by ECT's can provide insight into daily life disease burden and the control of asthma. Current guidelines for bronchoprovocation tests restrict both the use of reliever and maintenance asthma medication before an exercise challenge to prevent false-negative testing, as both have significant acute bronchoprotective properties. However, restricting maintenance medication before an ECT may be less appropiate to evaluate EIB symptoms in daily life when a diagnosis of asthma is well established. Rigorous of maintenance medication before an ECT according to guidelines may lead to overestimation of the real, daily life asthma burden and lead to an inappropiate step-up in therapy. The protection against EIB offered by the combined acute and chronic bronchoprotective effects of maintenance medication can be properly assessed whilst maintaining them. This may aid in achieving the goal of unrestricted participation of children in daily play and sports activities with their peers without escalation of therapy. When considering a step down in medication, a strategic wash-out of maintenance medication before an ECT aids in providing objective support of potential discontinuation of maintenance medication.

Predictive modeling of COPD exacerbation rates using baseline risk factors.

Background:Demographic and disease characteristics have been associated with the risk of chronic obstructive pulmonary disease (COPD) exacerbations. Using previously collected multinational clinical trial data, we developed models that use baseline risk factors to predict an individual’s rate of moderate/severe exacerbations in the next year on various pharmacological treatments for COPD.Methods:Exacerbation data from 20,054 patients in the ETHOS, KRONOS, TELOS, SOPHOS, and PINNACLE-1, PINNACLE-2, and PINNACLE-4 studies were pooled. Machine learning was used to identify predictors of moderate/severe exacerbation rates. Important factors were selected for generalized linear modeling, further informed by backward variable selection. An independent test set was held back for validation.Results:Prior exacerbations, eosinophil count, forced expiratory volume in 1 s percent predicted, prior maintenance treatments, reliever medication use, sex, COPD Assessment Test score, smoking status, and region were significant predictors of exacerbation risk, with response to inhaled corticosteroids (ICSs) increasing with higher eosinophil counts, more prior exacerbations, or additional prior treatments. Model fit was similar in the training and test set. Prediction metrics were ~10% better in the full model than in a simplified model based only on eosinophil count, prior exacerbations, and ICS use.Conclusion:These models predicting rates of moderate/severe exacerbations can be applied to a broad range of patients with COPD in terms of airway obstruction, eosinophil counts, exacerbation history, symptoms, and treatment history. Understanding the relative and absolute risks related to these factors may be useful for clinicians in evaluating the benefit: risk ratio of various treatment decisions for individual patients.Clinical trials registered with www.clinicaltrials.gov (NCT02465567, NCT02497001, NCT02766608, NCT02727660, NCT01854645, NCT01854658, NCT02343458, NCT03262012, NCT02536508, and NCT01970878)

Long-term predictors of severe exacerbations and mortality in a cohort of well-characterised adults with asthma

BackgroundWe aimed to explore long-term predictors of severe exacerbations and mortality in adults with well-characterised asthma.Study design and methodsAdults (aged ≥ 15) with an objectively verified diagnosis of asthma were recruited from a Danish respiratory outpatient clinic between 1974 and 1990. All individuals were followed in Danish registries for vital status, hospital admissions for asthma and cause of death until end of 2017. Predictors of exacerbations were obtained from a repeated measures model. Standardised mortality rates (SMR) for all-causes were compared with the Danish background population. Hazard ratios for mortality were obtained from a cox proportional hazards model in a two-step process.ResultsAt baseline, the cohort comprised 1071 patients (mean age 38, SD 16, 61% women), of whom 357 (33%) died during follow-up, with 93 (26%) dying from asthma (primary diagnosis). We found an SMR of 1.24 (95% CI 1.11–1.37, p < 0.001) for all-cause mortality. Baseline predictors for asthma-related death and repeated severe exacerbations were increasing age, ever smoker, FEV1 < 80% pred., high blood eosinophils, longer duration of symptoms and use of SABA > twice daily. Being non-atopic, having a positive histamine challenge test and symptoms more than twice a week were also predictors of repeated exacerbations.ConclusionsMarkers of poor asthma control, including high use of SABA, are predictors of long-term exacerbation rate and mortality over 30 years in patients with well-characterised asthma. Improving asthma control, including lung function and reducing use of reliever medication, is vital for improving the long-term outcome of asthma.

Is cannabis use associated with prescription psychotropic and pain reliever medication and other substance use among individuals aged 50+ with mental illness?

BackgroundDespite increasing rates of nonmedical and/or medical cannabis use in the 50+ age group, scant research exists on the associations between cannabis use and prescription medication use. In this study, we examined associations of use of prescription tranquilizers, sedatives, stimulants, and pain relievers, tobacco products, any/binge/heavy alcohol, and illicit drugs with cannabis use and use characteristics among U.S. adults aged 50+ years with past-year mental illness (n = 6454). MethodsData are from the 2015–2019 National Survey on Drug Use and Health (NSDUH). We used logistic regression models to examine associations of past-month use of each substance with (1) cannabis use among all those with past-year mental illness, and (2) cannabis use characteristics among cannabis users, controlling for severity of mental illness and sociodemographic and health characteristics. ResultsOf individuals aged 50+, 14.1 % had any past-year mental illness, and 9.7 % of those with mental illness, compared to 4.0 % of those without, reported past-month cannabis use. Compared to nonusers, cannabis users had higher odds of using each substance except antidepressants, with adjusted odds ratios ranging from 1.3 (sedatives) to 3.6 (illicit drugs). Compared to nonmedical cannabis users, medical users had 2–2.5 times higher likelihood of co-use of tranquilizers, sedatives, and prescription pain relievers but lower odds of binge and heavy alcohol use. ConclusionsCannabis users, especially medical cannabis users, are significantly more likely to use prescription psychotropic or pain medications. Healthcare professionals should assess for poly-substance use and potential adverse effects among older adults with mental illness.

Real-time effects of COVID-19 pandemic lockdown on pediatric respiratory patients.

ObjectiveA national lockdown was implemented in Israel to slow the viral spread of COVID‐19. We assessed the real‐time effects of the lockdown on disease expression and lifestyle modifications in pediatric patients with chronic respiratory disorders.MethodsAn anonymous electronic questionnaire was distributed during lockdown (March–May 2020) to caregivers of patients with chronic respiratory disorders. The primary outcome was change in disease expression and the secondary outcomes were changes in lifestyle and caregivers’ emotional status.ResultsThe clinical status of one‐third of the 445 participating patients (age 0–18 years) reportedly improved, including decreased respiratory symptoms (n = 133, 33%), exacerbation frequency (n = 147, 35%), and use of reliever medications (n = 101, 27.4%). The condition of ~10% of the patients worsened. Clinical improvement was noted mostly in young patients <5 years (p = .001), asthmatic patients (p = .033), and patients with multiple underlying respiratory disorders (p = .015). Patients whose condition significantly worsened were more likely to be >5 years (p < .001), had increased screen time, decreased physical activity, and shorter sleep duration compared to their younger counterparts (p = .008, <.001, and .001, respectively). Caregivers’ reports (n = 236 [58%]) of their own anxiety levels and perceptions of the patients’ elevated health risk were increased, regardless of the children's actual clinical status.ConclusionCOVID‐19 lockdown was associated with clinical improvement/stability for most of the surveyed children; however, their caregivers' anxiety level was heightened. An increased sedentary lifestyle was reported mostly in older children.

COPDCompEx: A novel composite endpoint for COPD exacerbations to enable faster clinical development

BackgroundFrequency of moderate and severe chronic obstructive pulmonary disease exacerbations is an important endpoint in clinical trials, but makes them large and lengthy when powered to evaluate it. We aimed to develop a composite endpoint (COPDCompEx) that could predict treatment effect on exacerbations, enabling the design of shorter early phase clinical trials requiring fewer patients. MethodsIn this post hoc analysis, data from 20 randomized controlled trials were used to develop and test COPDCompEx. Diary events were tested against predefined threshold values for peak expiratory flow, reliever medication use, and symptoms. A COPDCompEx event was defined as first occurrence of a diary event, a moderate or severe exacerbation, or a study dropout. Ratios of event frequency, treatment effect and future trial sample size were compared between COPDCompEx and moderate and severe exacerbations. FindingsAt 3 months, the proportion of patients experiencing COPDCompEx events increased over 3-fold versus exacerbations alone. All components contributed to COPDCompEx event rate. Treatment effects at 3 months were closely matched between COPDCompEx and exacerbations, and the large net gain in power substantially reduced the required sample size. InterpretationCOPDCompEx may be used to predict treatment effect on moderate and severe exacerbations of chronic obstructive pulmonary disease. This may enable the design of shorter Phase 2 clinical trials requiring fewer patients when compared with current exacerbation studies, with exacerbations as a key Phase 3 endpoint. This would, therefore, allow more efficient decision-making with reduced burden and risk to study participants.

Allergic rhinitis and asthma symptoms in a real-life study of MP-AzeFlu to treat multimorbid allergic rhinitis and asthma

BackgroundAsthma affects up to nearly 40% of patients with allergic rhinitis (AR). Poor control of AR symptoms is associated with poor asthma control. The goal of this study was to evaluate the effect of AR treatment with MP-AzeFlu on symptoms of AR as well as symptoms of asthma.MethodsThis prospective study used a visual analog scale (VAS) to assess symptoms of AR and asthma before and after treatment with MP-AzeFlu (Dymista®; azelastine hydrochloride plus fluticasone propionate; 1 spray in each nostril twice daily for 2 weeks). Participants suffered from moderate-to-severe AR according to Allergic Rhinitis and its Impact on Asthma criteria, with acute AR symptoms (AR-VAS scores ≥ 50 mm) on inclusion day. In addition to symptom assessment, patients recorded the impact of AR symptoms on quality-of-life measures before, during, and at the conclusion of the treatment period (approximately 14 days). Patients self-reported change in frequency of their usage of asthma reliever medication on the last day of treatment.ResultsOf 1103 study participants, 267 (24.2%) had comorbid asthma. These participants reported using a mean of 5.1 puffs of asthma reliever medication in the week before treatment with MP-AzeFlu. A total of 81.8% of patients with comorbid asthma responded to AR therapy (AR-VAS < 50 mm on at least 1 study day). Among patients with AR and comorbid asthma, MP-AzeFlu was associated with improved VAS scores across all study parameters, including AR symptom severity, asthma symptom severity, sleep quality, daily work or school activities, daily social activities, and daily outdoor activities. Asthma symptom severity decreased from a mean of 48.9 mm to 24.1 mm on the VAS. Self-reported frequency of asthma reliever medication use was reduced for 57.6% of participants (n = 139/241).ConclusionMP-AzeFlu used to relieve AR symptoms was associated with reduced asthma symptom VAS scores and frequency of asthma reliever medication usage. Changes in overall symptoms of AR and asthma were correlated.

Bronchial thermoplasty versus mepolizumab: Comparison of outcomes in a severe asthma clinic.

BT and interleukin-blocking monoclonal antibodies are both effective therapies for severe asthma, but there have been no direct comparisons between the two treatments. The aim of this study was to compare the efficacy and safety of BT and mepolizumab, in a real-world setting. Patients with severe asthma despite optimized inhaler therapy were drawn from a severe asthma clinic in a tertiary hospital. Every patient commencing therapy with BT or mepolizumab was prospectively included in a national registry. At predetermined assessment points over a 12-month period, assessments were made of ACQ, spirometry, oral corticosteroid requiring exacerbations, reliever medication and maintenance oral corticosteroid use. A total of 91 patients with severe asthma participated: mean ACQ score 3.5 ± 1.0, FEV1 51.4 ± 17.7%, maintenance oral steroids 48.3% and 11.5 ± 10.0 inhalations/day reliever therapy. Forty-seven patients received mepolizumab and 44 received BT. Baseline characteristics were similar except significantly higher blood eosinophil count in the mepolizumab group. At 12 months, there were no differences between treatment outcomes for ACQ (1.9 ± 1.3 mepolizumab vs 1.7 ± 1.3 BT), exacerbation rate (0.9 ± 1.1 vs 0.9 ± 1.5), reduction in reliever use (-6.3 ± 10.5 vs -5.0 ± 8.8 puffs/day) or reduction in oral corticosteroids (-3.3 ± 7.5 vs - 5.8 ± 6.7 mg/day). The FEV1 improved equally (160 ± 290 vs 150 ± 460 mL). Readmission or prolonged admission was observed in 18.2% of BT patients, whilst 25.5% of mepolizumab patients had discontinued treatment at 12 months, 14.9% due to an adverse event or non-compliance. The results suggest that BT is as efficacious as mepolizumab for the treatment of severe asthma.

Variability in airway inflammation, symptoms, lung function and reliever use in asthma: anti-inflammatory reliever hypothesis and STIFLE study design.

Asthma is a chronic inflammatory airway disease. Increase in airway inflammation is hypothesised to contribute to worsening of asthma symptoms and deterioration in lung function, resulting in the use of reliever medication. Short-acting β2-agonists only treat the symptoms, whereas an anti-inflammatory reliever is believed to treat both symptoms and the underlying inflammation, thereby arresting the progression to an exacerbation. As-needed budesonide/formoterol as an anti-inflammatory reliever reduces the risk of severe exacerbations. However, supporting mechanistic evidence has not yet been described, specifically the temporal dynamics of parameters including airway inflammation, over time and during asthma worsening.The STIFLE study aims to characterise daily variability in airway inflammation, symptoms, lung function and reliever use in people with asthma. This phase IV, open-label, parallel-group, multicentre, exploratory study will enrol 60–80 adult patients with asthma receiving low- or medium-dose inhaled corticosteroids/long-acting β2-agonists (EudraCT identifier number 2018-003467-64). Participants will be randomised 1:1 to either as-needed budesonide/formoterol dry-powder inhaler or salbutamol reliever for 24 weeks, in addition to their maintenance therapy. Daily data will be captured for fractional exhaled nitric oxide, spirometry, asthma symptoms and medication use using devices connected to a smartphone via the STIFLE application. STIFLE will thereby enable not only characterisation of the variability of airway inflammation and clinical outcomes in relation to asthma worsening, but also elucidate the effect of as-needed budesonide/formoterol on airway inflammation against a background of daily maintenance therapy.

Clinical Factors Associated With Overuse of Asthma Reliever Medication.

Our aim was to evaluate the relationship between the clinical factors of asthma and the use of reliever medication. We performed an observational cross-sectional study in Spain. The study population comprised patients aged ≥12 years diagnosed with persistent asthma according to the criteria of the Global Initiative for Asthma and receiving maintenance treatment for at least 12 months. Use of reliever medication was classified as low use of reliever medication (LURM) (≤2 times/wk) and high use of reliever medication (HURM) (≥3 times/wk). A variety of clinical variables and patient-reported outcomes (PROs) were recorded (eg, scores on the Asthma Control Questionnaire-5 [ACQ-5] and Test of Adherence to Inhalers [TAI]). A total of 406 patients were recruited. Mean (SD) age was 44.3 (17.9) years, and 64% were women. Reliever medication was used ≤2 times/wk in 76.1%. Bivariate analysis showed that HURM was related to smoking habit, unscheduled emergency department visits, hospital admissions, higher doses of inhaled corticosteroid, and night awakenings in the previous 4 weeks (P<.001). The multivariate analysis showed a higher risk of using reliever medication in smokers and former smokers, when the number of night awakenings increased, in cases of self-perception of partially controlled or uncontrolled asthma, or when asthma is uncontrolled according to the ACQ-5. Our study identifies the potential of poor use of reliever medication in the last week as an alarm signal for disease-related parameters such as exacerbations, poor asthma control, and disease severity.

Direct costs of overdiagnosed asthma: a longitudinal, population-based cohort study in British Columbia, Canada

ObjectivesA current diagnosis of asthma cannot be objectively confirmed in many patients with physician-diagnosed asthma. Estimates of resource use in overdiagnosed cases of asthma are necessary to measure the burden...

Does adherence to inhaled corticosteroids predict asthma-related outcomes over time? A cohort study.

Inhaled corticosteroids (ICS) adherence is important for asthma management. Current evidence on the impact of ICS adherence on outcomes is mostly based on correlational analyses of between-person data. Although it is widely acknowledged that asthma outcomes fluctuate over time, evidence on predictors of within-person change is scarce. We aimed to quantify these fluctuations and the longitudinal relationships between ICS adherence and outcomes at both between- and within-person levels.A prospective cohort of persistent asthma patients in France and the UK (n=847, age 6-40 years) provided 3756 reports over up to 2 years via computer-assisted telephone interviews and text messages on ICS adherence, asthma control, reliever medication use and exacerbations. We examined adherence-outcome relationships via longitudinal models, controlling for confounders, including severity.Considerable within-person variability was found for exacerbations (91%), asthma control (59%) and reliever use (52%); 431 (11.5%) reports signalled exacerbations and 2046 (54.5%) poor control. At between-person level, patients with higher average adherence were more likely to report asthma control (OR 1.25, 95% CI 1.06-1.47), but not asthma exacerbations (OR 0.99, 95% CI 0.87-1.12) or lower reliever use (b -0.0004, 95% CI -0.089-0.088). At within-person level, higher-than-usual adherence was associated with higher concomitant reliever use (b 0.092, 95% CI 0.053-0.131) and lower subsequent reliever use (b -0.047, 95% CI -0.005- -0.088); it was unrelated to asthma control (OR 0.93, 95% CI 0.84-1.02) or exacerbations (OR 1.04, 95% CI 0.94-1.16).Patients maintaining high ICS adherence over time have better asthma control. Temporarily increasing ICS adherence tends to be simultaneous to higher reliever use and reduces reliever use later on. Causes of within-person variation in outcomes require more investigation.

Safety and Effectiveness of Bronchial Thermoplasty When FEV1 Is Less Than 50%

Randomized clinical trials of bronchial thermoplasty (BT) were conducted in patients with a baseline FEV1 greater than 50%. There is a paucity of data regarding BT in patients with more severe obstruction, and consequently these patients are often excluded from receiving BT. The purpose of this study was to compare safety and efficacy outcomes in a large cohort of patients with an FEV1 less than 50%with those of a cohort of less obstructed patients. Consecutive patients with severe asthma were drawn from the Australian BT Registry. Patients were grouped into (1) those with a baseline prebronchodilator FEV1 %predicted< 50%(n= 32) or (2) those with an FEV1≥ 50%(n= 36). Adverse outcomes were defined as (1) remaining in hospital longer than the planned 24-hour admission posttreatment or (2) being readmitted to hospital for any cause within 30days of a treatment. Efficacy outcomes were evaluated 6months after BT. More severely obstructed patients were no more likely to have experienced any adverse event. Significant improvements in Asthma Control Questionnaire score, exacerbation frequency, reliever medication use, and requirement for daily oral steroids were observed in both groups, and were of a similar degree. This study demonstrates that BT can confidently be offered to patients with asthma with an FEV1 that is 30%to 50%of predicted without risk of more frequent or more severe adverse events, and with the expectation of the same degree of response as patients with better lung function.

Symptoms and perception of airway obstruction in asthmatic patients: Clinical implications for use of reliever medications

Asthma causes the unpleasant sensation of breathlessness (dyspnea) caused by airway obstruction. Patients with poor perception of airway obstruction are at risk of delay in seeking medical attention and undertreatment, which can lead to avoidable deaths. Conversely, those with heightened perception are at risk of overtreatment and iatrogenic adverse effects with reliever medications, anxiety, and unnecessary use of health care resources. We sought to review evidence about symptom misperception in asthmatic patients and how to identify and manage affected patients, particularly with regard to reliever medications. We conducted a systematic literature search for studies of perception of airway function in asthmatic patients. We searched the OVID (Medline and Medline [R] in process [PubMed]), Embase, and Adisearch/Odyssey databases, restricting our search to human studies published in English from 1990-2018, with no restrictions on age, sex, or racial origin. We found that both underperception and overperception assessed during induced bronchoconstriction or bronchodilation or during changes in airway resistance were common across all age groups and that aging, disease severity, smoking, sex, ethnicity, psychologic factors, and medication are all associated with differences in perception. Importantly, airway inflammation was associated with impaired perception and a history of severe or near-fatal asthma. We also identified knowledge gaps, such as whether an individual patient's perception varies over time and the influence perception has on patients' use of reliever medication. We found that abnormal perception of airway obstruction has important clinical implications for the management of patients with asthma.

Role of the pharmacist in improving inhaler technique and asthma management in rural areas in Jordan.

IntroductionPharmacists can have a valuable role in educating patients on correct inhaler technique leading to improved asthma management. Rural areas can benefit from the role of the pharmacist considering the barriers found in attending primary health-care facilities.ObjectivesThis study aimed to assess the impact of inhaler technique education delivered by pharmacists on patients’ inhaler technique, Asthma Control Test (ACT) score, forced expiratory volume in the first 1 second (FEV1%), and reliever use (puffs/day).MethodsA pre–post interventional study was conducted over 6 months from February 2017 to July 2017 in rural areas in Jordan. Asthma patients visiting respiratory clinics and using metered dose inhaler (MDI) or turbuhaler (TH) controlled medication were randomly recruited. Inhaler technique was assessed via published checklists. The ACT, FEV1%, and reliever use (puffs/day) were assessed. Patients were educated on inhaler technique via demonstration with return demonstration education. All assessments were repeated 3 months post education.ResultsA total of 103 (TH, n=44; MDI, n=59) patients were recruited (mean age=46.5±13.5), 74% females. Patients reported an overuse of their reliever (5.1±4.2 puffs/day). Only 2 patients (1.9%) had well-controlled asthma, while the rest had either moderately (19.4%) or poorly (78.6%) controlled asthma. Patients using the MDI achieved 3.03±4.30 ACT score improvement (p<0.001), which is a clinically significant improvement in control. Patients using the TH achieved a statistically significant improvement of 2.07±4.72 (p=0.031). FEV1% improved significantly for MDI users (p=0.005) but not for TH users (p=0.097). Reliever use decreased significantly for MDI and TH users.ConclusionAsthmatic patients living in rural areas in Jordan reported poor inhaler technique, ACT scores, and FEV1% scores and high use of reliever medications. Pharmacist-led educational intervention resulted in improved inhaler technique scores, ACT scores, and FEV1% scores and lowered reliever use over time.