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Does body mass index influence responsiveness to inhaled corticosteroids in persistent asthma?

Although the relationship between asthma and obesity has been extensively explored, the effect of body mass index (BMI) on the dose-response relationship to inhaled corticosteroids (ICS) has received little attention.

OBJECTIVE: To assess the dose-response of inhaled budesonide on outcome measures of asthma between overweight and normal weight patients with persistent asthma.

METHODS: Seventy-two patients with mild to moderate persistent asthma from a post hoc analysis of previously reported trial data were divided into 2 groups: overweight, BMI 25 kg/m(2) or higher; normal weight, BMI less than 25 kg/m(2). Each group received 4 weeks' treatment with inhaled (hydrofluoroalkane) budesonide 200 μg/day then 800 μg/day with ICS washout pretreatment. Outcome measures forced expiratory volume in 1 second (FEV(1)), fractional exhaled nitric oxide (FeNO), methacholine PC20, total daily asthma symptom score, and overnight urinary cortisol/creatinine ratio were performed at baseline and after each dose.

RESULTS: Significantly greater improvements were seen in the normal weight group for both FeNO and symptom responses at 0 to 200 μg and 0 to 800 μg ICS doses (as change from baseline), compared with the overweight group: FeNO 0 to 200 μg, P = .002; 0 to 800 μg, P = .045; symptoms 0 to 200 μg, P = .002; 0 to 800 μg, P = .013. A trend also was seen toward attenuated cortisol suppression in overweight subjects at 0 to 800 μg (P = .06), but no significant difference was seen at either dose in FEV(1) and methacholine PC20 between weight groups.

CONCLUSION: Overweight patients with persistent asthma may have attenuated symptom and FeNO dose responses to inhaled budesonide compared with normal weight patients with asthma, with no differences in FEV(1) or methacholine PC20 between groups. Attenuated cortisol suppression in the overweight group may be the clue to this difference, alluding to reduced peripheral lung deposition or absorption in overweight patients with asthma.

Uncontrolled asthma and factors related to morbidity in an impoverished, rural environment.

Asthma disproportionately affects children living in impoverished communities; however, factors related to asthma morbidity among impoverished rural children have not been adequately described.

OBJECTIVE: To examine factors associated with asthma morbidity among rural children living in the Arkansas Delta region.

METHODS: We performed a cross-sectional investigation of 109 rural children with asthma enrolled in public schools in the Arkansas Delta region. A questionnaire format and home inspection were used to examine participant, caregiver, and home characteristics.

RESULTS: The median age of the study participants was 9 years, 83% were African American, and 71% had an annual household income of $20,000 or less. Ninety-eight percent of participants were insured, and most fit the criteria for uncontrolled asthma, yet only 23% reported taking inhaled corticosteroids. Transportation problems were cited by 20%. In the past 4 weeks, more than 50% reported rescue medication use or exercise limitations of 2 or more days per week or nocturnal symptoms of more than 2 nights per month. Emergency department visits in the past 6 months were reported by 28%, and 43% reported an unscheduled physician's visits for asthma in the past 3 months. Sixty-four percent had 1 or more positive allergen skin test results, and allergic sensitization was associated with exposure to dust mite, dog, mouse, and cockroach allergens in the home.

CONCLUSION: Asthma morbidity was high among this cohort of atopic asthmatic children in the Arkansas Delta. Overuse of rescue medications and underuse of inhaled corticosteroids were prevalent even though the population was highly insured and had frequent health care use. Future asthma health initiatives should focus on the unique challenges associated with translating national guidelines-based care to rural pediatric populations.

Mometasone furoate nasal spray increases the number of minimal-symptom days in patients with acute rhinosinusitis.

Acute rhinosinusitis (ARS) is triggered by viral or, uncommonly, bacterial infection, causing inflammatory symptoms for ≤12 weeks.

OBJECTIVE: To investigate effects of mometasone furoate nasal spray (MFNS) vs amoxicillin and placebo on minimal-symptom days.

METHODS: A double-blind, parallel-group, placebo- and active-controlled 15-day study randomly assigned patients 12 years of age or older to MFNS 200 μg twice daily, MFNS 200 μg once daily, amoxicillin 500 mg 3 times daily, or placebo. Patients had baseline rhinosinusitis major symptom score (MSS; combined rhinorrhea, postnasal drip, congestion, sinus headache, facial pain) of ≥5 and ≤12 (maximum: 15) for 7 to 28 days; scores were similar among groups. Minimal-symptom days and minimal-congestion days were defined post hoc by average am/pm MSS ≤4 and average am/pm congestion ≤1.

RESULTS: MFNS twice daily (n = 234) showed more minimal-symptom days vs placebo (n = 246) (62.69% vs 50.33%; P < .0001) or amoxicillin (n = 248) (54.35%; P = .0040). The MFNS QD was associated with numerically more minimal-symptom days than amoxicillin or placebo (54.72%; P ≤ .8982). MFNS was associated with more minimal-congestion days than placebo (72.97%, 67.73%, and 56.67% for twice daily, once daily, and placebo; P < .0001, each vs placebo) and MFNS BID with more minimal-congestion days than amoxicillin (72.97% vs 64.15%; P = .0007). Median time to first minimal-symptom day sustained until study end was 8.5 days for MFNS BID vs. 11 for placebo (P = .0085).

CONCLUSION: MFNS 200 μg twice daily significantly increased minimal-symptom days vs amoxicillin or placebo in patients with ARS. Results of this intranasal corticosteroids (INS) therapy indicate it can improve outcomes and potentially reduce inappropriate antibiotic use.

Long-term low-dose antibiotics in recalcitrant chronic rhinosinusitis: a retrospective analysis.

In recalcitrant Chronic RhinoSinusitis (CRS) treatment with intranasal corticosteroids, short-term antibiotics and even sinus surgery is frequently insufficient. Long-term low-dose administration of antibiotics has been suggested as a treatment option in these patients. We analysed the outpatient clinic population treated with different long-term low-dose antibiotics at the AMC Amsterdam.

PATIENTS AND METHODS: Eligible patients, who were treated with trimethoprim-sulfamethoxazole or macrolides, were retrospectively identified from our outpatient clinic in 2009. The two main outcome measures were sinonasal complaints and nasal endoscopic findings. A 5-point grading scale was used to score the results compared with the pre-treatment situation. This was measured at several time-points during, and after the antibiotic course, and at the end of the follow-up term.

RESULTS: Seventy-six patients were included, 53 per cent had asthma and all of them had undergone sinus surgery. Seventy-eight per cent showed improvement of the symptoms, and 84 per cent demonstrated improvement of the sinonasal mucosa at the end of the course. No significant difference was found between the trimethoprim-sulfamethoxazole and macrolide group.

DISCUSSION: Long-term low-dose treatment with antibiotics seems to improve CRS symptoms and the appearance of the sinonasal mucosa on nasal endoscopy. However, at this stage, strong conclusions are immature because no placebo-group has been included. Despite increasing use of long-term low-dose treatment of recalcitrant CRS in referral centres, hard clinical evidence is lacking. More research is urgently required.

Fetal and infant origins of asthma.

Previous studies have suggested that asthma, like other common diseases, has at least part of its origin early in life.

Low birth weight has been shown to be associated with increased risks of asthma, chronic obstructive airway disease, and impaired lung function in adults, and increased risks of respiratory symptoms in early childhood. The developmental plasticity hypothesis suggests that the associations between low birth weight and diseases in later life are explained by adaptation mechanisms in fetal life and infancy in response to various adverse exposures. Various pathways leading from adverse fetal and infant exposures to growth adaptations and respiratory health outcomes have been studied, including fetal and early infant growth patterns, maternal smoking and diet, children's diet, respiratory tract infections and acetaminophen use, and genetic susceptibility. Still, the specific adverse exposures in fetal and early postnatal life leading to respiratory disease in adult life are not yet fully understood.

Current studies suggest that both environmental and genetic factors in various periods of life, and their epigenetic mechanisms may underlie the complex associations of low birth weight with respiratory disease in later life. New well-designed epidemiological studies are needed to identify the specific underlying mechanisms.

This review is focused on specific adverse fetal and infant growth patterns and exposures, genetic susceptibility, possible respiratory adaptations and perspectives for new studies.

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