De-implementation of inappropriate inhaled corticosteroid use in patients with COPD in general practice, results of a mixed methods study

Patterns of inhaled corticosteroid use and asthma control in the Childhood Asthma Management Program Continuation Study

IntroductionAdherence to asthma medications is generally low and may be detrimental to clinical outcomes (Robijn et al, 2019).1 Poor adherence is characterized by underuse of inhaled corticosteroids (ICS), often accompanied...

Risk of cataracts in the Childhood Asthma Management Program Cohort

Inhaled corticosteroids (ICS) are widely used to treat chronic obstructive pulmonary disease (COPD), often early in the course of disease and at higher doses. The safety concerns for osteoporosis and fractures with long-term use of ICS could particularly affect post-menopausal women with decreased bone density. To date, the studies have been inconclusive, with none evaluating the differential effect in men and women. Using the Quebec universal health insurance databases, we formed a new-user cohort of COPD patients initiating treatment with ICS or other therapies during 1990-2005, followed through 2007 for a fracture of the hip or of upper extremity. A Cox model with time-dependent ICS exposure was used to estimate the rate ratio of fracture associated with duration and dose of ICS use, adjusted for age, sex, disease severity and co-morbidity, also assessing whether the risk differed between men and women. The cohorts included 139,119 users of ICS and 169,745 non-users, of which 19,396 had a fracture (51% of the hip and 49% of the humerus, radius or ulna) during a mean 4.1 years of follow-up (incidence rate 15.4/1000/year). Any use of ICS was not associated with an increased rate of fracture (rate ratio (RR) 1.00; 95% confidence interval (CI): 0.97-1.03). The rate was elevated with longer than 4 years of ICS use at daily doses of 1000 mcg or more of fluticasone-equivalent (RR 1.10; 95% CI 1.02-1.19). This risk increase did not differ between men and women or among the different ICS agents. In conclusion, long-term use of inhaled corticosteroids in COPD at high doses is associated with a modest increase in the risk of fracture of the hip and upper extremities, similarly so for men and women.

The most prevalent children's chronic disease worldwide is asthma which has notable negative impacts on patients' and parent's quality of life. Daily inhaled corticosteroids (ICS) therapy is a preferred controller choice. This study was conducted on 148 parents of asthmatic children to establish parents' perception of illness and fear of inhaled corticosteroids using B-IPQ and TOPICOP questionnaires. Children were in the majority male (66.9%), older than five years (58.8%), with comorbidities, and family history of atopy. Parents were female, with a mean age of 38, employed, and with a history of some form of corticosteroid use. Most parents were not afraid of ICS usage (71.6%). Unemployed parents and parents who had no medical education had a statistically significantly higher fear of using ICS (p = 0.002, p = 0.03). A child's illness affects the parents' lives and parents who are afraid of using ICS react more emotionally to the child's illness. Better understanding and less concerned about child's disease are parents of children with controlled asthma. The parents' perspective of children's asthma will affect the duration and dose of ICS treatment they will give to their children and directly influence the level of asthma control.

Introduction: Despite the fewer side effects of inhaled corticosteroids, there are indication to show that the use of inhaled steroids may have a possible risk factor for ocular hypertension and glaucoma.Aim of this study was to identify whether an association existed between duration of inhaled corticosteroid use and elevated intraocular pressure (IOP) or open-angle glaucoma (OAG) in patients with asthma and chronic obstructive pulmonary disease (COPD).Materials and methods: A total of 214 asthma and COPD patients using inhaled corticosteroids (ICS) at least for the last 6 months were included in the study.The participants were divided into 2 groups based on the duration of ICS use; Groups A had 81 patients, who were using inhaled corticosteroids between 6 months to 1 year and group B had 133 patients, who were using inhaled corticosteroids for more than 1 year.Results: Mean IOP of group A was 14.79 and group B was 16.77 (p<0.05).In group A, 3 (3.7%)patients had IOP 21 whereas in group B, 16 (12.03%)patients had IOP 21.No one had OAG in group A, whereas 3 (2.25%)patients had OAG in group B. Conclusion: These findings suggest an association between the duration of use of inhaled corticosteroids and a finding of elevated IOP or glaucoma in subjects with asthma and COPD.

For patients with persistent asthma, inhaled corticosteroids (ICS) are a mainstay of controller therapy. These medications are usually prescribed to be taken daily and have been shown to be associated with decreased asthma morbidity. Adherence to daily treatment is very low in many populations in the United States. The purpose of this study is to evaluate the seasonal use of ICS prescription filling as reactive behavior primarily after an asthma exacerbation in a pediatric population. The study population is a subgroup of the Tennessee Asthma and Bronchiolitis Study. The children in this study were enrolled in Tennessee Medicaid (TennCare). The subjects had asthma and were 6 to 9 years of age during the years 2005 to 2010. Prescription filling was determined using claims data, and asthma exacerbations were defined by use of systemic rescue corticosteroids (RCS). In this cohort of 13,114 children with asthma, ICS and RCS filling were highly seasonal and trended with fall and winter peaks in asthma exacerbations. Prescription refilling was very low, with an average of three ICS fills per child who filled at least one during the study period. Among these children, 54.1% (7,096) had an asthma exacerbation during the study period. Among ICS users, 68.5% (3,441/5,020) had a disease exacerbation. ICS filling occurred overwhelmingly on the same day as RCS fills. The seasonal filling patterns of ICS coincide with asthma exacerbations. ICS adherence is low and inconsistent in this population of children with asthma. Increased adherence to ICS, particularly before the seasonal virus epidemics, could greatly reduce asthma morbidity.

Objective Asthma is a common chronic respiratory disease affecting people of all ages, but little is known about age-related differences in treatment strategies. The present study aims to explore age-related differences in inhaled corticosteroid (ICS) use and place of asthma management. Methods All Danish adults with a registered secondary care asthma diagnosis or active treatment (>1 redemption of ICS within 365 days) in 2021 were included. Individuals with chronic obstructive pulmonary disease and individuals who migrated or died during the observation period were excluded. Danish national registries provided all treatment data. Results A total of 184,565 patients with asthma (median age 57 [IQR 43–69], 59% female) were included. Overall, 15.7% of the asthma population was treated with high (>800–1600 budesonide-equivalent ug/day) or supratherapeutic (>1600 budesonide-equivalent ug/day) doses of ICS, and the proportion increased with age before reaching a plateau from age 56 onwards (lowest: 18–45 years, 9.7%; highest: 66–75 years, 18.9%; p < .001). Significantly fewer of the patients in the oldest age group were seen in specialist care (highest: 56–65 years, 18.9%; lowest: >86 years, 11.4%; p < .001), and 77.3% of patients exposed to high or supratherapeutic doses of ICS were managed only in primary care. Conclusion The prevalence of high- and supratherapeutic ICS exposure was higher among patients ≥56 years, and when exceeding 76 years of age, a smaller proportion were managed in secondary care. With an increased focus on adverse effects of high-dose ICS treatment and earlier initiation of other treatments, our findings will, hopefully, facilitate less age inequity in asthma management.

As an initial investigation to determine whether or not inhaled corticosteroids can be discontinued, we evaluated the results of discontinuation in patients who had been well controlled with inhaled corticosteroids for more than one year prior to this study. The average dose of BDP which the patients had been inhaling at the start of this study was 365 micrograms/day. To determine the effect of discontinuing inhaled corticosteroids, we compared the patients' peak expiratory flow rates and the frequency of beta-agonist use between the 4-week observation period and follow-up periods of varying duration. Only three out of twenty patients enrolled were able to maintain their discontinuation of BDP, while the remaining seventeen patients restarted after a mean period of 30.8 days. Mean peak flow values began to fall during the first week after discontinuation, and decreased morning peak flow values became significant in the 2nd, 3rd and 4th weeks. The mean peak flow value during the observation period was 85.2% of each patient's personal best, but had dropped to 68.8% of this level just before restarting inhaled corticosteroid. The frequency of beta-agonist use during the study period (2.99 +/- 3.39 times a day) was significantly higher than during the observation period (1.94 +/- 2.95 times a day). This finding strongly suggests that the patients' asthmatic conditions had become unstable during the study period. These results suggest that any decision to discontinue the use of inhaled corticosteroid, even in well controlled patients with chronic asthma, should be taken with great care.

This study was conducted to assess the validity of parental reported use of inhaled corticosteroids (ICS) in children. ICS users were identified within the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study and the PIAMA pharmacy sub-cohort which is nested within the PIAMA study. Complete medication histories were available for the first 8 years of life for children within the PIAMA pharmacy sub-cohort. Parental reported ICS use was measured by using data from questionnaires. ICS use in the pharmacy records was determined by using the Anatomical Therapeutic Chemical (ATC) codes. The proportion of overall agreement and kappa statistics with their corresponding 95% confidence intervals were calculated to quantify agreement between self-reported medication use and pharmacy prescription data. At all ages overall agreement was very high (>97%) and Cohen's kappa's ranged from 0.80 to 0.88 which also reflects excellent agreement between parental reported use of ICS and pharmacy prescription data. Our finding suggests that parental report of medication use is a reliable source of data to asses ICS use in children. The questionnaire-based medication data collected within the PIAMA study can be used to study asthma medication use in a large group of children.

Rationale: The use of inhaled corticosteroids (ICS) is associated with increased pneumonia risk, but the risk of invasive pneumococcal disease (IPD) associated with ICS is not characterized.Objectives: The aim was to test the hypothesis that the use of ICS increases the risk of IPD.Methods: Cases were persons 20–65 years of age included in a Swedish national registry of invasive infection caused by Streptococcus pneumoniae classified as any IPD as well as the subset of IPD with pneumonia. The case index date was the day the infection was diagnosed. Six control subjects for each case (matched for sex, age, and region) were selected from the Swedish National Population Registry and were assigned the index date of their corresponding case. Current and past users of ICS were defined by the last prescriptions dispensed within 60 or 61–365 days of the index date. Nonusers were defined as those with no dispensed prescription the last 365 days. Current users were characterized by use of fluticasone or budesonide. We used conditional logistic analysis, including matching and covariates, to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of IPD, IPD with pneumonia, and IPD without pneumonia associated with current or past use of ICS.Results: Current use of ICS increased the risk for IPD and IPD with pneumonia (OR, 1.71; 95% CI, 1.39–2.10 and OR, 1.94; 95% CI, 1.53–2.47, respectively), but there was no statistical association between current use of ICS and IPD without pneumonia (OR, 1.18; 95% CI 0.78–1.80). Past use of ICS increased the risk for IPD and IPD with pneumonia but not for IPD without pneumonia. Among current ICS users, the odds for IPD were similar for budesonide (OR, 1.34; 95% CI, 1.14–1.57) and fluticasone (OR, 1.41; 95% CI, 1.04–1.90). Among current ICS users, the odds for IPD with pneumonia were slightly higher but of similar magnitude for both budesonide and for fluticasone.Conclusions: ICS use is associated with an increased risk of IPD and IPD with pneumonia. The risk is driven by IPD with pneumonia. We found similar risks for budesonide and fluticasone.

Preterm birth is associated with respiratory morbidity later in life, including asthma. Previous studies have mainly focused on asthma in early childhood in children born extremely preterm. In this study, we examined the risk of asthma in a national cohort of schoolchildren grouped according to degree of immaturity expressed as completed gestational weeks at birth. This was a register study in a Swedish national cohort of 1 100 826 children 6 to 19 years old. Retrieval of at least 1 prescription of inhaled corticosteroids (ICS) during 2006 was used as the main indicator for asthma. Logistic regression was used to test hypotheses, with adjustment for multiple socioeconomic and perinatal indicators. Degree of immaturity, expressed as completed gestational weeks at birth, had an inverse dose-response relationship with ICS use. Compared with children born between 39 and 41 weeks' gestation, the odds ratio for ICS use increased with the degree of prematurity, from 1.10 (95% confidence interval: 1.08-1.13) for children born in weeks 37 to 38, to 2.28 (95% confidence interval: 1.96-2.64) for children born in weeks 23 to 28, after adjustment for confounders. The increase in ICS use with decreasing gestational age at delivery was similar in boys and girls, and declined with older age. Preterm birth increased the risk of ICS use in these 6- to 19-year-olds by degree of immaturity, from extremely preterm to early term birth.

There have been concerns that systemic corticosteroid use is associated with pregnancy-induced hypertension (PIH) and diabetes mellitus. However, the relationship between inhaled corticosteroids (ICSs) and the risk of PIH has not been fully examined, and there was no study investigating the association between ICS use and the development of gestational diabetes mellitus (GDM). The aims of the study are to determine whether the use of ICSs during pregnancy increases the risk of PIH and GDM in women.We conducted 2 nested case-control studies utilizing the nationwide insurance claims database of the Health Insurance Review and Assessment Service (Seoul, Republic of Korea), in which 1,306,281 pregnant women who delivered between January 1, 2009 and December 31, 2011 were included. Among them, PIH cases and GDM cases were identified and matched controls were included. Conditional logistic regression analyses adjusted by other concomitant drugs use during and before pregnancy and confounding covariates including comorbidities were performed.Total 43,908 PIH cases and 219,534 controls, and 34,190 GDM cases and 170,934 control subjects were identified. When other concomitant drugs use during pregnancy was adjusted, ICS use was associated with an increased rate of PIH (adjusted odds ratio, 1.40 [95% CI, 1.05–1.87]). ICS medication possession ratios and cumulative doses were associated with an increased risk of PIH. However, the statistical significance was not found in other models. In both unadjusted and adjusted multivariable models, ICSs use was not associated with increase in the risk of GDM.ICSs use is not associated with an increased risk of PIH and GDM.

Atopy Modifies the Association Between Inhaled Corticosteroid Use and Lung Function Decline in Patients with Asthma

The burden of severe asthma on patients, especially on those with concomitant chronic rhinosinusitis with nasal polyps (CRSwNP), is substantial. Treatment intensification with oral corticosteroids is a common strategy for managing severe asthma exacerbations; however, prolonged exposure to systemic corticosteroids is associated with multisystem toxicity. This study aimed to quantify the association between oral corticosteroid use and annual asthma-related costs in patients with severe asthma with or without CRSwNP. This pharmacoeconomic analysis was based on data from the Severe Asthma Network in Italy (SANI) registry. Asthma-related costs were estimated in the context of the Italian healthcare system and included exacerbations requiring treatment intensification, unplanned visits, admissions to hospital and emergency/intensive care units, and lost workdays. For each item, the mean annual cost per patient was estimated based on national tariffs and the frequency of the event. To quantify the association between oral corticosteroid treatment and costs, the study cohort was stratified according to oral corticosteroid use in the 1-year preceding inclusion in the SANI registry. A total of 669 patients from the SANI registry were included in the present analysis, 255 of whom had concomitant CRSwNP. Corticosteroid use was associated with significantly higher annual disease-related costs per patient compared with no corticosteroid use. Compared with the overall study cohort and patients without CRSwNP, patients with CRSwNP had higher disease-related costs (higher by €1307 and €1869, respectively). Use of corticosteroids, in particular systemic corticosteroids, is associated with an increase in asthma-related costs. The concomitant presence of CRSwNP impacts negatively on costs. This study suggests that a thorough analysis of costs, expected benefits, and occurrence of adverse events is required when selecting treatment intensification strategies for managing uncontrolled severe asthma.