Relationship between asthma medication and antibiotic use.

STUDY OBJECTIVES: Increasing morbidity due to asthma and antimicrobial resistance among human pathogens are both major public-health concerns. Numerous studies describe the overuse of antibiotics in general populations and underuse of anti-inflammatory medications by asthmatic patients. However, little is known about the relationship between asthma medication and antibiotic use in asthmatics. Specifically, we tested the hypothesis that higher use of bronchodilator and anti-inflammatory medication by asthmatics, as a marker of problematic asthma, is associated with greater antibiotic use. We also test the hypothesis that physicians who are low prescribers of anti-inflammatory medications are high prescribers of antibiotics. DESIGN: We conducted a retrospective cohort study evaluating asthma medication and antibiotic use by children and adults with asthma and the prescribing of these medications by primary-care physicians. SETTING/PATIENTS: Subjects were continuously enrolled asthma patients aged 6 to 55 years receiving care in an urban, group-model, health maintenance organization. INTERVENTIONS: None. MEASUREMENT AND RESULTS: Main outcome measures were (1) antibiotic use by asthmatics stratified by low, moderate, and high bronchodilator use; (2) antibiotic use by asthmatics stratified by no, intermittent, and long-term anti-inflammatory use; and (3) correlation between physician-level anti-inflammatory agent to bronchodilator ratio (AIF:BD) and their rate of antibiotic prescribing. We found that (1) high bronchodilator users received 1.72 antibiotics per person-year (95% confidence interval [CI], 1.62 to 1.83), whereas low bronchodilator users received 1.23 antibiotics per person-year (95% CI, 1.19 to 1.27; p < 0.0001); (2) long-term users of anti-inflammatory agents received 1.85 antibiotics per person-year (95% CI, 1.76 to 1.95), whereas those not receiving an anti-inflammatory agent received 0.95 antibiotics per person-year (95% CI, 0.90 to 1.00; p < 0.0001); and (3) despite variations in physician AIF:BDs and antibiotic prescribing, respectively, these measures were not correlated. CONCLUSIONS: Antibiotic use and asthma medication use are positively associated in a cohort of asthma patients. Greater effort is needed to define the appropriate role of antibiotics in asthma management.     

Long-term control medication use and asthma control status among children and adults with asthma

Background: Uncontrolled asthma decreases quality of life and increases health care use. Most people with asthma need daily use of long-term control (LTC) medications for asthma symptoms and to prevent asthma attacks. Ongoing assessment of a person's level of asthma control and medication use is important in determining the effectiveness of current treatment to decrease the frequency and intensity of symptoms and functional limitations. Objective: To assess the use of LTC medication among children and adults with current asthma and identify contributing factors for LTC medication use. Methods: We used the 2006–2010 Behavioral Risk Factor Surveillance System (BRFSS) child and adult Asthma Call-back Survey (ACBS) data to assess the level of asthma control and LTC medication use. Asthma control was classified as well controlled and uncontrolled using guideline-based measures. We used multivariable logistic regression models to identify contributing factors for LTC medication use and having uncontrolled asthma. Results: Among persons with current asthma, 46.0% of children and 41.5% of adults were taking LTC medications and 38.4% of children and 50.0% of adults had uncontrolled asthma. Among children who had uncontrolled asthma (38.4%), 24.1% were taking LTC medications and 14.3% were not taking LTC medications. Among adults who had uncontrolled asthma (50.0%), 26.7% were taking LTC medications and 23.3% were not taking LTC medications. Conclusions: Using BRFSS ACBS data to assess the level of asthma control and LTC medication use can identify subpopulations of persons with asthma who receive suboptimal treatment, for which better asthma-related medical treatment and management are needed.     

The association of psychiatric medication use with adherence in patients with HIV

Over two million new cases of HIV infection will occur annually, worldwide. Triple drug anti-retroviral therapy (ART) decreases the viral load in patients with HIV, helping to stop progression of HIV infection to AIDs. Our study assessed how pharmacologic treatment for mental health issues affects medication adherence and viral load in patients with HIV. We conducted a retrospective chart review of 163 patients with HIV who had at least 2 visits at the HIV-clinic at Ascension St. John Hospital. Data were collected on demographics, medications, CD4 counts and viral loads. Data were analyzed using Student’s t-test, the χ² test, the Mann–Whitney U test and logistic regression. “Poor Compliance” was defined as at least 2 consecutive visits with a CD4 count <200?µL and/or with viral load ≥100?IU/ml. Patients taking antidepressants were less likely to have poor compliance than those not on anti-depressants (6.3% vs. 22.3%, p?=?0.04). A similar association was found for patients taking any psychiatric drug (7.0% vs. 23.5%, p?=?0.02). On multivariable analysis, the odds of poor compliance were 6.3 times higher in patients who stopped HIV therapy for greater than one week between visits (p?=?0.004) and 3.6 times lower in patients taking any psychiatric medication (p?=?0.05).     

大气细颗粒物对血管内皮功能的影响及阿托伐他汀的干预研究

目的:观察大气环境中细颗粒物对血管内皮功能的影响,探索细颗粒物作用于心血管疾病的途径和机制,同时使用阿托伐他汀进行干预,观察药物对内皮损伤的作用。方法:将细颗粒物使用0.9%氯化钠配制成浓度为4000μg/ml的悬浮液,对人脐静脉血管内皮细胞(Endothelial cells,EC-304)进行染毒,染毒终浓度为400μg/ml,观察细颗粒物对EC-304细胞存活率、细胞内丙二醛(Malondial dehyde,MDA)、细胞裂解液中超氧化物歧化酶(Superoxide dismutase,SOD)及细胞上清液中一氧化氮(Nitrous oxide,NO)等的影响。同时使用阿托伐他汀钙药物进行干预,在染毒细胞中加入0.1μmol/L,1μmol/L和10μmol/L剂量浓度的阿托伐他汀钙,测定药物对上述指标的影响。结果:细颗粒物有机提取物染毒后,EC-304的存活率明显下降、细胞上清液MDA明显升高、细胞内SOD及细胞上清液中NO较对照组明显下降(P<0.01)。染毒后加入阿托伐他汀钙能明显改善细颗粒物对血管内皮细胞的毒性作用,使EC-304上清液MDA较对照组明显下降,而细胞存活率、细胞内SOD及细胞上...     

Differences in asthma diagnosis and medication use in children living in Germany and the Netherlands.

AIM: To compare diagnosis and treatment between German and Dutch children with asthmatic symptoms at the age of 5-6 and 7-8 years, and the use of anti-asthma medication at 7-8 years of age. METHODS: Parents of 4462 children participated in two surveys, in 1995 and 1997. All 465 children identified with current asthmatic symptoms at the age of 5-6 (May 1995) or at 7-8 years of age (May 1997) were sent a third more detailed questionnaire (October 1997). RESULTS: Asthma diagnosis was more prevalent in Dutch children with current asthmatic complaints (50-60%), whereas over 90% of the German children with current asthmatic complaints had been diagnosed with bronchitis. Inhaled beta(2)-agonists were more frequently used by Dutch children compared to German children (67.3% vs. 45.6% p < 0.01) as were inhaled steroids (38.9% vs. 7.0% p < 0.01). Instead, German children more often used sodium cromoglycate or nedocromil as anti-inflammatory medication as compared with Dutch children (42.1% vs. 11.5% p < 0.01). CONCLUSIONS: Differences in diagnosis rates for asthma and bronchitis between German and Dutch children most likely result from differential labelling of complaints, and probably lead to differences in treatment practice, indicating possible undertreatment of German children with inhaled steroids.     

Near-fatal asthma in South Australia:descriptive features and medication use

Background: Self-reported prior morbidity levels and medication use among survivors of a near-fatal asthma attack (NFA) were studied.
Aims: To identify deficiencies in asthma management and opportunities for intervention.
Methods: A hundred and twenty-seven consecutive patients aged 15 years or more presenting with a NFA to accident and emergency departments of teaching hospitals were interviewed.
Results: High levels of morbidity due to asthma were reported. Most cases (79%) reported symptoms occurring at least weekly in the three months before their NFA. A mean of 20.8 days was reportedly lost from work, school or other usual daily activity in the 12 months before these events. Regular use of beta agonist as nebuliser solution was reported by 27% of cases, increasing to 34.5% in response to increased symptoms, while 41% reported use of nebulised beta agonist in response to the NFA event. Less than half of all cases (46%) reported using an inhaled corticosteroid on a regular basis. Oral corticosteroids were used by 33% of cases at times of increased symptoms in the preceding 12 months. However, only 7% of cases reported initiating or increasing oral corticosteroids at the time of the NFA.
Conclusions: Despite high levels of prior asthma morbidity, regular preventive inhaled corticosteroid use was not widespread in this series of NFA asthmatics. By comparison, over-reliance on regular beta agonist medication was common. Oral corticosteroids were rarely commenced in response to the NFA.     

Patterns of corticosteroid medication use: non-adherence can be effective in milder asthma.

AIMS: To identify specific patterns of corticosteroid use and examine their relationship with asthma outcomes. METHODS: An adherence questionnaire was developed and applied in a population-based observational survey; this compared unscheduled care visits and asthma quality of life for adherent and non-adherent patient groups within 176 patients from a semi-rural UK practice. RESULTS: Three main patterns of medication use were identified: Regular; Regular-but-less (Low-Dosing); and Symptom-Directed variation. For mild-to-moderate asthma (BTS treatment step 2), non-adherence produced acceptable outcomes, not significantly different from outcomes for adherent patients. For more severe asthma, regular adherence was more effective, resulting in significantly less unscheduled visits. CONCLUSIONS: The results suggest that flexible 'symptom-directed' medication use and patient-initiated dose reduction may be viable alternatives to regular medication for a number of lower severity patients. For milder asthma, clinicians should perhaps focus their efforts on patients with poor asthma outcomes, rather than poor adherence.     

Comparing inhaled ultrafine versus fine zinc oxide particles in healthy adults: a human inhalation study

RATIONALE: Zinc oxide is a common, biologically active constituent of particulate air pollution as well as a workplace toxin. Ultrafine particles (< 0.1 microm diameter) are believed to be more potent than an equal mass of inhaled accumulation mode particles (0.1-1.0 microm diameter). OBJECTIVES: We compared exposure-response relationships for respiratory, hematologic, and cardiovascular endpoints between ultrafine and accumulation mode zinc oxide particles. METHODS: In a human inhalation study, 12 healthy adults inhaled 500 microg/m3 of ultrafine zinc oxide, the same mass of fine zinc oxide, and filtered air while at rest for 2 hours. MEASUREMENTS AND MAIN RESULTS: Preexposure and follow-up studies of symptoms, leukocyte surface markers, hemostasis, and cardiac electrophysiology were conducted to 24 hours post-exposure. Induced sputum was sampled 24 hours after exposure. No differences were detected between any of the three exposure conditions at this level of exposure. CONCLUSIONS: Freshly generated zinc oxide in the fine or ultrafine fractions inhaled by healthy subjects at rest at a concentration of 500 microg/m3 for 2 hours is below the threshold for acute systemic effects as detected by these endpoints.     

Response of human alveolar macrophages to ultrafine,fine, and coarse urban air pollution particles

In the lower airways, macrophages are important regulators of inflammation and indispensable in their antimicrobial activities. Thus, air pollution particles, which modulate airway macrophage host defenses may, in susceptible individuals, increase severity of inflammatory and infectious disease. In the present study, size fractionated, ultrafine (UF), fine (PM0.1-2.5), and coarse (PM2.5-10) particulate matter (PM) were collected from 2 urban sites in the Netherlands, and were compared for effects on human alveolar macrophages (AM). Inflammatory cytokine production, phagocytosis, and expression of phagocyte receptor CD11b were assessed in particle-exposed AM. Interleukin (IL)-6 levels induced by PM2.5-10 (20411 pg/mL) were > 10-fold higher than induced by PM0.1-2.5 (1781 pg/mL). Levels induced by PM0.1-2.5 were 2- to 3-fold higher than induced by UF (770 pg/mL) when cells were exposed to the same particle mass. Cytokine induction by the PM was inhibited by antibody to CD14 and required the presence of serum for optimal stimulation, implying that bacterial products or endotoxin were stimulatory moieties in both coarse and fine particulate matter. Phagocytosis of opsonized yeast was inhibited by coarse more than by fine PM, as was yeast-induced oxidative burst. Coarse particles decreased CD11b expression more than fine PM. The UF did not affect these functions. Taken together, these results suggest that PM recognition by human AM involves receptors evolved to recognize microbial cell structures, and that microbial products preferentially found in the coarse particle fraction of PM may be involved in inflammatory events and decreased pulmonary defenses associated with exposure to pollution particles.     

Residential proximity fine particles related to allergic sensitisation and asthma in primary school children

BACKGROUND: Fine particulate matter has been linked to allergies by experimental and epidemiological data having used aggregated data or concentrations provided by fixed-site monitoring stations, which may have led to misclassification of individual exposure to air pollution. METHODS: A semi-individual design was employed to relate individual data on asthma and allergy of 5338 school children (10.4 +/- 0.7 years) attending 108 randomly chosen schools in 6 French cities to the concentrations of PM2.5 (fine particles with aerodynamic diameter 2.5 microm) assessed in proximity of their homes. Children underwent a medical visit including skin prick test (SPT) to common allergens, exercise-induced bronchial (EIB) reactivity and skin examination for flexural dermatitis. Their parents filled in a standardised health questionnaire. RESULTS: After adjustment for confounders and NO2 as a potential modifier, the odds of suffering from EIB and flexural dermatitis at the period of the survey, past year atopic asthma and SPT positivity to indoor allergens were significantly increased in residential settings with PM2.5 concentrations exceeding 10 microg/m3 (WHO air quality limit values). The relationships were strengthened in long-term residents (current address for at least 8 years). CONCLUSIONS: Findings support the hypothesis that changes in allergy prevalence observed in recent decades might be partly related to interactions between traffic-related air pollution and allergens. Further longitudinal investigations are needed to corroborate such results.     

Measurement properties of an asthma symptom and rescue medication use diary

Abstract

Introduction: Assessment of symptoms and rescue medication use are well-established endpoints for clinical trials evaluating asthma treatment. Objective: To evaluate the measurement properties of an asthma symptom and rescue medication use (ASRMU) diary for clinical trials involving asthma patients aged ≥12 years. Methods: Interviews with 35 patients were conducted to confirm the importance of key concepts in the ASRMU diary. Scores of symptom and rescue medication use were converted to symptom-free days (SFD) and rescue-free days (RFD). Test–retest reliability and equivalence (based on intra-class correlation coefficients [ICCs]) between paper-and-pencil and electronic (eDiary) versions were evaluated in a prospective study in 47 patients. Responsiveness of the ASRMU diary was evaluated through differences in percentage of SFD and of RFD by treatment group in eight asthma clinical trials that assessed inhaled corticosteroids (ICS) and long-acting β₂-agonists (LABA), alone or in combination. A ninth placebo-controlled study calculated effect sizes. Minimal important differences (MID) were determined using anchor-based methods from two trials and by interviewing 11 patients. Results: Patient interviews supported content validity for the ASRMU diary. Test–retest reliability was acceptable for SFD (ICC:0.70–0.75), but varied for RFD (ICC:0.58–0.78). Paper-and-pencil and eDiary modes of administration were equivalent (SFD, ICC?=?0.84; RFD, ICC?=?0.70). ICS/LABA had the largest percentage of SFD and RFD, followed by monotherapy and then placebo. MIDs were 7.7–14.7% for SFD and 8.4–15.6% for RFD. Conclusions: The ASRMU diary captures the disease-specific concepts of greatest importance to asthma patients and provides important information for asthma diagnosis and treatment evaluation.     

Formoterol Turbuhaler as reliever medication in patients with acute asthma.

The aim of this study was to compare the efficacy and safety of formoterol versus salbutamol as reliever medication in patients presenting at an emergency dept with acute asthma. A randomised, double-blind, double-dummy, parallel group study was performed in four Australian emergency treatment centres. The study included a total of 78 adult patients (mean baseline forced expiratory volume in one second (FEV1) 1.83 L; 59% predicted) with acute asthma. Based on the expected dose equivalence of formoterol Turbuhaler 4.5 microg (delivered dose) and salbutamol pressurised metered-dose inhaler 200 microg (metered dose), patients received a total of formoterol Turbuhaler 36 microg (delivered) or salbutamol pressurised metered-dose inhaler with spacer 1,600 microg (metered), divided into two equal doses at 0 and 30 min. FEV1, peak expiratory flow and systemic beta2-agonist effects were monitored for 4 h. The primary variable was FEV1% pred at 45 min. At 45 min, mean increases in FEV1 expressed in % pred were 6.6% and 9.3%, respectively, with a small adjusted mean difference in favour of salbutamol (3.0%, 95% confidence interval -2.0-8.0). Transient increases in systemic beta2-agonist effects occurred predominantly with salbutamol, although no significant treatment differences were observed. Eight patients discontinued due to adverse events. In this study of patients presenting at emergency depts with acute asthma, formoterol Turbuhaler 36 microg was well tolerated and, as rescue therapy, had an efficacy that was not different from that of salbutamol pressurised metered-dose inhaler with spacer 1,600 microg in the number of patients studied.     

Traditional and patient-centred outcomes with three classes of asthma medication.

Lung function is commonly used as the primary endpoint in asthma clinical trials, but it may not reflect changes which are important to patients. The present study compared changes in, and relationships between, traditional and patient-centred end-points during treatment with three classes of asthma medication. Subjects with mild-to-moderate asthma were randomised to double-blind, double-dummy crossover treatment with eformoterol 12 microg b.i.d. or montelukast 10 mg q.d., then single-blind treatment with fluticasone 250 microg b.i.d./placebo capsules, with 6-week treatment periods and 1-week washouts. Individual "traditional" end-points (symptoms, reliever use, forced expiratory volume in one second per cent predicted, morning peak expiratory flow, airway hyperresponsiveness) and "patient-centred" end-points (asthma control questionnaire, quality of life, patient global assessments) were assessed. Principal component analysis and linear modelling were used to explore overall rank orders for treatment, and relationships between outcomes. A total of 58 subjects were randomised. The rank order of benefit from eformoterol and fluticasone differed for three factors derived from principal component analysis (eformoterol>fluticasone for symptom/reliever use factor, fluticasone>eformoterol for lung function factor, eformoterol=fluticasone for patient-centred factor). Montelukast was ranked third for all three factors. A significant relationship between patient-based variables and lung function was found only for montelukast treatment. In asthma treatment, traditional end-points do not fully capture patient-centred benefits, and the relationship between end-points differs with medication class.     

Causative and contributive factors to asthma severity and patterns of medication use in patients seeking specialized asthma care

STUDY OBJECTIVES: (1) To assess the prevalence of specific factors considered causative or contributive to asthma in a population of patients seen in a specialized asthma clinic, and to determine whether any of these factors were associated with more severe disease; and (2) to assess the utilization of inhaled steroids by asthma severity in this population and compare it with published guidelines of the National Heart, Lung, and Blood Institute (NHLBI). DESIGN, SETTING, AND PATIENT POPULATION: We conducted a retrospective chart review of new patients seen in a specialized asthma treatment center over a 2.5-year period and recorded the prevalence of 14 causative or contributive factors, the severity of asthma, and the intensity of treatment with inhaled corticosteroids in each patient. Patients were grouped as mild asthma vs moderate/severe asthma and compared by chi(2) analysis and stepwise logistic regression to determine whether certain factors were associated with more severe asthma. MEASUREMENTS AND RESULTS: The average number of factors recorded was 2.9 +/- 1.8 in the mild group (+/- SD) and 3.5 +/- 1.6 in the moderate/severe asthma group. This difference was statistically significant (p = 0.014). Increasing age, male gender, symptomatic gastroesophageal reflux disease (GERD), and chronic sinusitis were independently associated with more severe asthma. Suboptimal use of inhaled corticosteroids was more common in patients with mild persistent asthma, but suboptimal dosing of inhaled corticosteroids was equally common in mild and moderate/severe asthma. No relationship was found between allergen sensitization combined with exposure to cats, dogs, dust mite, or molds and more severe asthma. CONCLUSIONS: This study confirms earlier studies showing that symptomatic GERD and chronic sinusitis are important comorbid conditions in patients with asthma, both being associated with greater asthma severity. This study further shows that the doses of inhaled corticosteroids used for treatment of asthma fall short of NHLBI guidelines in the majority of patients regardless of asthma severity.