The Burden of Severe Asthma in France: A Case-Control Study Using a Medical Claims Database.

BACKGROUND: Severe asthma (SA) is defined by treatment intensity. The availability of national databases allows accurate estimation of the prevalence, long-term outcomes, and costs of SA. OBJECTIVE: To provide accurate information on SA, focusing on comorbidities, mortality, health care resource consumption, and associated costs. METHODS: A cohort of patients with SA identified in 2012 was extracted from a French representative claims database and followed for 3 years. Their characteristics, comorbidities, mortality, and direct costs were compared with a matched control group without asthma. RESULTS: A total of 690 patients with SA were matched to 2070 patients without asthma (mean age, 61 years; 65.7% women). The prevalence of SA was estimated to be 0.18% to 0.51% of the French adult population. Comorbidities were more frequent in patients with SA (73.9% suffered from cardiovascular disease vs 54.3% in controls; P < .001). A total of 58.7% of patients with SA used oral corticosteroids (OCS) in 2012 with a mean intake of 3.3 boxes/year/patient and 9% received ≥6 dispensings of OCS. A total of 6.7% were treated by omalizumab. Patients with SA were more frequently hospitalized (33.2% vs 19.7%; P < .001), more frequently consulted a general practitioner (97.8% vs 83.9%; P < .001) (9.8 ± 6.8 vs 6.2 ± 5.3 consultations/year; P < .001), and 31% have consulted a private respiratory physician. Compared with controls, 3-year cumulative mortality was higher in SA (7.1% vs 4.5%; P = .007). Direct medical cost was $9227 versus $3950 (P < .001) mostly driven by medication costs. CONCLUSIONS: The prevalence of SA in the French adult population is at least 18 of 10,000. Burden of disease is high with respect to comorbidities, mortality, and asthma-related health care resource use.

Defining the "Frequent Exacerbator" Phenotype in COPD: A Hypothesis-Free Approach.

BACKGROUND: The COPD "frequent exacerbator" phenotype is usually defined by at least two treated exacerbations per year and is associated with a huge impact on patient health. However, existence of this phenotype and corresponding thresholds still need to be formally confirmed by statistical methods analyzing exacerbation profiles with no specific a priori hypothesis. The aim of this study was to confirm the existence of the frequent exacerbator phenotype with an innovative unbiased statistical analysis of prospectively recorded exacerbations. METHODS: Data from patients with COPD from the French cohort in Exacerbations of COPD Patients (EXACO) were analyzed using the KmL method designed to cluster longitudinal data and receiver operating characteristic (ROC) curve analysis to determine the best threshold to allocate patients to identified clusters. Univariate and multivariate analyses were performed to study characteristics associated with different clusters. RESULTS: Two clusters of patients were identified based on exacerbation frequency over time, with 2.89 exacerbations per year on average in the first cluster (n = 348) and 0.71 on average in the second cluster (n = 116). The best threshold to distinguish these clusters was two moderate to severe exacerbations per year. Frequent exacerbators had more airflow limitation, symptoms, and health-related quality of life impairment. A simple clinical score was derived to help identify patients at risk of exacerbations. CONCLUSIONS: These analyses confirmed the existence and clinical relevance of a frequent exacerbator subgroup of patients with COPD and the currently used threshold to define this phenotype.

Clinical characteristics and quality of life in women with COPD: an observational study.

BACKGROUND: The impact of COPD on patient's quality of life is well established, but gender differences have received little attention. METHODS: To describe factors associated with the health-related quality of life by gender: A cross-sectional observational study (NCT01007734) was conducted in COPD patients followed by pulmonologists. The first patient included had to be a woman. Data concerning the patient, COPD and their management were collected by the physician. The patient had to fill in several questionnaires: Saint-George Hospital respiratory Questionnaire (SGRQ-C), and motivation to quit smoking. RESULTS: Four hundred and thirty patients were included: mean age 63.9 ± 11.3 years; 57.4% were women. Women were significantly younger than men (61.9 vs. 66.6) and their tobacco use was lower (37.1 vs. 40.4 PY). Cardiovascular comorbidities were more frequent in men while osteoporosis, anxiety and depression were frequent in women. The frequency of cough, sputum and the severity of dyspnea did not differ significantly between genders. Lung function impairment was less severe in women than in men (mean FEV1 52% predicted normal vs. 47. 8%). Anxiety score was higher (score 9.8 vs. 7.1) and quality of life (SGRQ-C) more impaired in women (scores 50.6 vs. 45.4; p < 0.02) than in men. Moreover, in multivariate analysis, chronic sputum was associated with higher SGRQ-C scores in women but not in men. CONCLUSIONS: This study underlines that despite less airflow limitation, quality of life is more impacted by chronic sputum in women than in men.

Do asthmatic smokers benefit as much as non-smokers on budesonide/formoterol maintenance and reliever therapy? Results of an open label study.

BACKGROUND: Studies with inhaled corticosteroids (ICS) in smoking asthmatics have mostly shown poorer treatment responses than in non-smoking asthmatics. METHODS: EuroSMART, an open, randomised, 6-month study, compared budesonide/formoterol (Symbicort (®) Turbuhaler(®))(h) maintenance and reliever therapy (Symbicort SMART(®)) at two maintenance doses of budesonide/formoterol (160/4.5 µg), 1 × 2 and 2 × 2, in patients with asthma who were symptomatic despite treatment with ICS ± long-acting ß(2)-agonists. The 8424 randomised patients included 886 smokers (11%; aged <40 years or with a smoking history <10 pack-years if older), who were compared with a propensity-matched group of non-smokers. At baseline, smokers had lower post-bronchodilator peak expiratory flow, lower peak flow reversibility and used more reliever medication per day. Severe asthma exacerbations were counted and changes in five-item Asthma Control Questionnaire (ACQ-5) scores from baseline calculated. RESULTS: There were 48 and 47 exacerbations in smokers and non-smokers, respectively. Mean time to first severe exacerbation was not statistically different between the two groups. The mean change in ACQ-5 score was significantly greater in non-smokers. Considering the two treatment options there was a statistically significant prolonged time to first severe exacerbation with 2 × 2 versus 1 × 2 in the smokers, but not in the non-smokers. In smokers, the reductions in ACQ-5 scores, asthma symptoms, use of as-needed medication and awakenings were also all significant in favour of 2 × 2 with similar or greater changes than in smokers treated with 1 × 2. CONCLUSION: Asthmatic patients with a limited smoking history benefit from treatment with budesonide/formoterol maintenance and reliever therapy with dosing 2 × 2 being superior to 1 × 2.

Is the patient's baseline inhaled steroid dose a factor for choosing the budesonide/formoterol maintenance and reliever therapy regimen?

OBJECTIVE: Baseline inhaled corticosteroid (ICS) dose may be a factor for prescribers to consider when they select a budesonide/formoterol maintenance and reliever therapy regimen for symptomatic asthmatics. METHODS: A 6-month randomized study compared two maintenance doses of budesonide/formoterol 160/4.5 µg, 1 × 2 and 2 × 2, plus as needed, in 8424 asthma patients with symptoms when treated with ICS ± an inhaled long-acting ß(2)-agonist (LABA). In the total study population, 1339 (17%) were high-dose ICS (HD) users (≥ 1600 µg/day budesonide). This HD stratum was compared with the rest of the study population, divided into low-dose (LD; 400 µg/day) and medium-dose strata (MD; 401-1599 µg/day) with regard to severe asthma exacerbations and mean changes in five-item Asthma Control Questionnaire (ACQ(5)) scores from baseline. RESULTS: In all three strata there were fewer exacerbations in the 2 × 2 treatment groups (yearly rates 0.268, 0.172 and 0.094) than in the 1 × 2 treatment groups (yearly rates 0.232, 0.138 and 0.764). In no stratum was the difference between the treatment groups statistically significant. There was no statistically significant difference in time to the first severe exacerbation between the treatments 2 × 2 and 1 × 2 in the HD group (hazard ratio 0.944, p = 0.75). The adjusted mean changes in ACQ(5) scores in the HD, MD and LD strata were -0.89, -0.61 and -0.65, respectively, with 1 × 2 treatment and -0.90, -0.74 and -0.76, respectively, with 2 × 2 treatment. In the MD and LD strata, the difference between doses was significant in favour of 2 × 2 (MD p < 0.0001; LD p = 0.004), but not in the HD stratum (p = 0.870). No difference in serious adverse events was seen. CONCLUSION: Compared with the LD and MD strata, the HD stratum patients had more exacerbations and a shorter time to first exacerbation. However, there were no differences in response between the 1 × 2 and 2 × 2 groups in any of the strata. This indicates that patients using budesonide/formoterol maintenance and reliever therapy, irrespective of baseline ICS dose, can be switched to 1 × 2 with its lower steroid load. ACQ(5) scores improved more in the HD stratum than in the MD and LD strata indicating, among other things, that HD patients were not overtreated at baseline.

The effect of an information leaflet upon knowledge and awareness of COPD in potential sufferers. A randomized controlled study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is markedly under-diagnosed, which may be related to the under-reporting of symptoms and poor awareness of the disease. We hypothesized that written information on COPD may help increase awareness of the disease in people at risk of developing it. OBJECTIVES: To evaluate the impact of an information leaflet sent by postal mail on the level of knowledge of COPD in subjects with or at risk of COPD. METHODS: A total of 860 subjects with or at risk of COPD were selected by using a phone questionnaire. All subjects who reported a known diagnosis of COPD, a chronic cough and sputum production, or a smoking history of at least 15 pack-years were eligible for selection. Their knowledge of COPD was assessed during a telephone interview (baseline). They were randomized into 2 groups, with only 1 group receiving the information leaflet, and were then contacted 3 months later for a second interview. The changes in the knowledge of COPD from baseline were compared between subjects who reported receiving and reading the leaflet (true sensitized group) and subjects to whom the leaflet was not sent (control group). RESULTS: At the follow-up interview, the proportion of patients who spontaneously mentioned 'respiratory difficulties', when asked about the meaning of COPD, significantly increased in the true sensitized group (+11.9%) compared with the control group (+2.6%, p < 0.05). In addition, the frequency of patients who cited lung function test as the primary diagnostic tool for COPD increased by +14.4% in the true sensitized group versus+2.0% in the control group (p < 0.05). However, there was no short-term leaflet-dependent improvement in smoking behaviour or utilization of health-care resources. CONCLUSIONS: This study shows that an information leaflet sent by postal mail to subjects with or at risk of COPD can significantly improve their knowledge of COPD; however, it has no significant impact on their behaviour.

Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial.

Nebulized budesonide has been used successfully to treat acute asthma exacerbation, and we hypothesized that it could also be effective for exacerbations of chronic obstructive pulmonary disease (COPD). In this multicenter, double-blind, randomized, placebo-controlled trial, the efficacy of nebulized budesonide (Pulmicort Respules/Nebuamp), oral prednisolone, and placebo was compared in 199 patients with acute exacerbations of COPD requiring hospitalization. Patients received from randomization (H(0)) to 72 h (H(72)), 2 mg of budesonide every 6 h (n = 71), 30 mg of oral prednisolone every 12 h (n = 62), or placebo (n = 66). All received standard treatment, including nebulized beta(2)-agonists, ipratropium bromide, oral antibiotics, and supplemental oxygen. The mean change (95% confidence interval) in postbronchodilator FEV(1) from H(0) to H(72) was greater with active treatments than with placebo: budesonide versus placebo, 0.10 L (0.02 to 0.18 L); prednisolone versus placebo, 0.16 L (0.08 to 0.24 L). The difference in FEV(1) between budesonide and prednisolone was not significant, -0.06 L (-0.14 to 0.02 L). The occurrence of serious adverse events was similar for all groups. Budesonide had less systemic activity than prednisolone as indicated by a higher incidence of hyperglycemia observed with prednisolone. Both budesonide and prednisolone improved airflow in COPD patients with acute exacerbations when compared with placebo. Nebulized budesonide may be an alternative to oral prednisolone in the treatment of nonacidotic exacerbations of COPD but further studies should be done to evaluate its long-term impact on clinical outcomes after an initial episode of COPD exacerbation.