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Timothy J Craig

Publications and source records attributed to Timothy J Craig.

27 records · Page 2Linked to original sources
PubMed2004

Inflammatory responses in allergic rhinitis: traditional approaches and novel treatment strategies.

Allergic rhinitis (AR) is associated with decreased learning, performance and productivity at work and school, as well as a reduced quality of life. With a staggering annual economic impact between 6 billion dollars and 8 billion dollars, AR affects 20% of the adult population and up to 40% of children. Effective therapy for allergic rhinitis requires understanding the pathophysiology of the disease, as well as the role of various inflammatory mechanisms. As such, various classes of medication are at the physicians' disposal to treat patients with allergic rhinitis. Among these are second-generation antihistamines and anticholinergic agents, intranasal corticosteroids, and mast cell stabilizers. Recently, montelukast, a leukotriene receptor antagonist, has been added to the modes of therapy approved by the US Food and Drug Administration for allergic rhinitis. For patients refractive to standard pharmacologic intervention, immunotherapy has shown some promising results. As newer strategies emerge, treatment regimens for allergic rhinitis should continue to improve not only daytime symptoms, but also nighttime symptoms and sleep with the fewest possible adverse effects.

Asthma↗
PubMed2003

Effect of topical nasal corticosteroids on patients with chronic fatigue syndrome and rhinitis.

BACKGROUND: Chronic fatigue syndrome (CFS) is a disabling illness of persistent fatigue. Recent studies have shown that patients with CFS have an increased prevalence of nonallergic rhinitis. Inflammation of the nasal passages due to allergic rhinitis can cause nasal congestion resulting in an increased number of sleep disturbances and daytime fatigue. While topical nasal corticosteroids have been shown to alleviate nasal obstruction effectively in patients with rhinitis who do not have CFS, it is unknown whether topical nasal corticosteroids will reduce CFS symptoms. STUDY OBJECTIVE: The purpose of this study is to determine whether topical nasal corticosteroids will reduce daytime sleepiness in patients with CFS and rhinitis. METHODS: Twenty-eight of 31 subjects with rhinitis and a diagnosis of CFS completed the double-blind, randomized, placebo-controlled trial. Two subjects failed screening, and 3 subjects withdrew from the study prior to its completion. Subjects were randomized according to Balaam's crossover design, and one of the following interventions was used for each group in the study: 8-week treatment with a topical nasal corticosteroid, 8-week treatment with a placebo saline spray, 4-week treatment with a topical nasal corticosteroid followed by a 4-week treatment with a placebo saline spray, or a 4-week treatment with a placebo saline spray followed by a 4-week treatment with a topical nasal corticosteroid. Data focusing on rhinitis symptoms, severity of chronic fatigue symptoms, and quality of life were gathered at biweekly office visits and with daily diaries. RESULTS: The results indicated that daytime sleepiness was reduced when patients with rhinitis and CFS were treated with topical nasal corticosteroids. The severity of associated CFS symptoms, specifically fatigue, muscle pain, postexertional fatigue, and daily activity, did not improve with treatment. CONCLUSION: Treating the symptoms of rhinitis in patients with CFS does not appear to alleviate daytime fatigue or associated nasal, musculoskeletal, or cognitive complaints. Therefore, it is unlikely that aggressive treatment of such symptoms with topical nasal corticosteroids will provide significant benefit to patients with CFS who do not have allergic rhinitis. These results indicate that the nonallergic rhinitis seen in patients with CFS may arise from a mechanism other than chronic inflammation.

Administration, Intranasal↗
PubMed2003

Improved immunotherapy with a rapid allergen vaccination schedule: a study of 137 patients.

Rapid allergen vaccination (RAV) is the updated term for what was previously called rush immunotherapy and rapid desensitization. RAV offers several advantages over traditional immunotherapy--that is, conventional allergen vaccination (CAV)--in terms of faster efficacy, better compliance, and cost-effectiveness. We used a 3-hour RAV protocol to treat 137 allergy patients. All patients were premedicated with either prednisone or prednisolone and an H1 antihistamine. Following the RAV procedure, all patients resumed a CAV schedule. Only six patients (4.4%) experienced a mild systemic reaction to RAV, and five (3.6%) experienced a mild systemic reaction to CAV 14 to 77 days later. All six patients who reacted to RAV quickly responded to treatment--in most cases, subcutaneous epinephrine and/or nebulized albuterol--and were sent home after a short period of observation. Compliance rates at 3, 6, and 12 months were 96.4, 94.2, and 75.9%, respectively, which is an improvement over rates previously reported for patients undergoing CAV therapy. We conclude that the 3-hour RAV protocol can be safely and successfully administered. Patients who undergo RAV are more compliant with their subsequent CAV regimen than are patients who do not undergo RAV because signs of clinical efficacy manifest almost immediately and because RAV is associated with substantially lower rates of systemic reactions. Moreover, RAV is associated with less morbidity and less expense. Our findings should encourage physicians who treat allergy patients to give further consideration to using RAV.

Adolescent↗
PubMed2002

Systemic effect comparisons of six inhaled corticosteroid preparations.

The goal of this study was to establish a reliable method to evaluate systemic bioavailability and to determine equisystemic effects (microgram dose producing equal systemic cortisol suppression) of inhaled corticosteroids (ICS). Steroid naive asthma subjects (n = 156) were enrolled at six centers. A 1-week doubling dose design was used for each of six ICS and matched placebos for a total of four doses. Systemic effect was evaluated by hourly plasma cortisol concentrations (8 P.M. to 8 A.M.), 12- and 24-hour urine cortisol concentrations, and a morning blood osteocalcin. The area under the concentration-time curve for hourly cortisol concentrations was the best outcome variable to assess systemic effect. For the six ICS and matching placebos (beclomethasone-chlorofluorocarbon [CFC], budesonide dry powder inhaler [DPI], fluticasone DPI, fluticasone-CFC metered dose inhaler [MDI], flunisolide-CFC, and triamcinolone-CFC), only the placebo group and fluticasone DPI did not demonstrate a significant dose-response effect. Thus microgram comparison of all ICS could only be performed at a 10% cortisol suppression: flunisolide-CFC - 936; triamcinolone-CFC - 787; beclomethasone-CFC - 548; fluticasone DPI - 445; budesonide DPI - 268; fluticasone-CFC MDI - 111. This study represents the first step in evaluation of ICS efficacy based on equisystemic (cortisol suppression) effects of a given ICS, rather than doses judged arbitrarily to be comparable on a microgram basis.

Administration, Inhalation↗
PubMed2002

Significant variability in response to inhaled corticosteroids for persistent asthma.

BACKGROUND: A clinical model is needed to compare inhaled corticosteroids (ICSs) with respect to efficacy. OBJECTIVE: The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs. METHODS: A 24-week, parallel, open-label, multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma. Benefit was assessed by improvements in FEV(1) and PC(20); risk was assessed by overnight plasma cortisol suppression. Thirty subjects were randomized to either beclomethasone dipropionate (BDP) 168, 672, and 1344 microg/day (n = 15) or fluticasone propionate (FP) 88, 352, and 704 microg/day (n = 15), both administered by means of a metered dose inhaler (MDI) with chlorofluorocarbon propellant via a spacer, in 3 consecutive 6-week intervals; this was followed by 3 weeks of FP dry powder inhaler (DPI) 2000 microg/day. RESULTS: Maximum FEV(1) response occurred with the low dose for FP-MDI and the medium dose for BDP-MDI and was not further increased by treatment with FP-DPI. Near-maximum methacholine PC(20) improvement occurred with the low dose for FP-MDI and the medium dose for BDP-MDI. Both BDP-MDI and FP-MDI caused dose-dependent cortisol suppression. Responsiveness to ICS treatment was found to vary markedly among subjects. Good (>15%) FEV(1) response, in contrast to poor (<5%) response, was found to be associated with high exhaled nitric oxide (median, 17.6 vs 11.1 ppb), high bronchodilator reversibility (25.2% vs 8.8%), and a low FEV(1)/forced vital capacity ratio (0.63 vs 0.73) before treatment. Excellent (>3 doubling dilutions) improvement in PC(20), in contrast to poor (<1 doubling dilution) improvement, was found to be associated with high sputum eosinophil levels (3.4% vs 0.1%) and older age at onset of asthma (age, 20-29 years vs <10 years). CONCLUSIONS: Near-maximal FEV(1) and PC(20) effects occurred with low-medium dose for both ICSs in the subjects studied. High-dose ICS therapy did not significantly increase the efficacy measures that were evaluated, but it did increase the systemic effect measure, overnight cortisol secretion. Significant intersubject variability in response occurred with both ICSs. It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study, such as prevention of asthma exacerbations.

Administration, Inhalation↗
PubMedDate not supplied

Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial.

BACKGROUND: The issue of whether regular use of an inhaled beta2-adrenergic agonist worsens airflow and clinical outcomes in asthma is controversial. Retrospective studies have suggested that adverse effects occur in patients with a genetic polymorphism that results in homozygosity for arginine (Arg/Arg), rather than glycine (Gly/Gly), at aminoacid residue 16 of the beta2-adrenergic receptor. However, the existence of any genotype-dependent difference has not been tested in a prospective clinical trial. METHODS: Patients with mild asthma, not using a controller medication, were enrolled in pairs matched for forced expiratory volume in 1 s (FEV1) according to whether they had the Arg/Arg (n=37; four of 41 matches withdrew before randomisation) or Gly/Gly (n=41) genotype. Regularly scheduled treatment with albuterol or placebo was given in a masked, cross-over design, for 16-week periods. During the study, as-needed albuterol use was discontinued and ipratropium bromide was used as needed. Morning peak expiratory flow rate (PEFR) was the primary outcome variable. The primary comparisons were between treatment period for each genotype; the secondary outcome was a treatment by genotype effect. Analyses were by intention to treat. FINDINGS: During the run-in period, when albuterol use was kept to a minimum, patients with the Arg/Arg genotype had an increase in morning PEFR of 23 L/min (p=0.0162); the change in patients with the Gly/Gly genotype was not significant (2 L/min; p=0.8399). During randomised treatment, patients with the Gly/Gly genotype had an increase in morning PEFR during treatment with regularly scheduled albuterol compared with placebo (14 L/min [95% CI 3 to 25]; p=0.0175). By contrast, patients with the Arg/Arg genotype had lower morning PEFR during treatment with albuterol than during the placebo period, when albuterol use was limited (-10 L/min [-19 to -2]; p=0.0209). The genotype-attributable treatment difference was therefore -24 L/min (-37 to -12; p=0.0003). There were similar genotype-specific effects in FEV1, symptoms, and use of supplementary reliever medication. INTERPRETATION: Genotype at the 16th aminoacid residue of the beta2-adrenergic receptor affects the long-term response to albuterol use. Bronchodilator treatments avoiding albuterol may be appropriate for patients with the Arg/Arg genotype.

Administration, Inhalation↗
PubMedDate not supplied

A practical approach to allergic rhinitis and sleep disturbance management.

Sleep quality can be significantly impacted by nasal congestion, a common symptom related to allergic rhinitis (AR). This may lead to decreased learning ability, productivity at work or school, and a reduced quality of life. A number of inflammatory cells and the release of inflammatory mediators lead to increased nasal congestion, causing disrupted sleep and subsequent daytime somnolence. Therefore, it is important to treat AR with medications that improve congestive symptoms without worsening sedation. Second-generation antihistamines and anticholinergic drugs are well tolerated but have little effect on congestion and therefore are limited in their ability to reduce AR-associated daytime somnolence. However, intranasal corticosteroids reduce congestion, improve sleep and sleep problems, and reduce daytime sleepiness, fatigue, and inflammation. Montelukast, a leukotriene receptor antagonist, has joined the approved therapies for AR. Montelukast significantly improves both daytime and nighttime symptoms. AR treatment should endeavor to improve daytime and nighttime symptoms, sleep, and productivity thereby improving quality of life.

Circadian Rhythm↗
PubMedDate not supplied

The effect of topical nasal fluticasone on objective sleep testing and the symptoms of rhinitis, sleep, and daytime somnolence in perennial allergic rhinitis.

Recent data suggested that daytime somnolence in patients with allergic rhinitis was secondary to disrupted sleep caused by nasal congestion. Medications, which decreased congestion, would be expected to improve sleep and daytime somnolence. Previously, we showed that nasal steroids improved all three symptoms. Presently, we have not performed objective sleep testing to determine if there is a correlation between subjective improvement of congestion, sleep, and daytime somnolence. The objective of this 8-week, double-blind, placebo-controlled study was to determine if topical nasal fluticasone is effective at decreasing subjective congestion and daytime somnolence and improving sleep and if this improvement correlated with a change in overnight sleep testing (polysomnography). We recruited 32 subjects with perennial allergic rhinitis and randomized them in a double-blinded, cross-over fashion, to receive placebo or fluticasone (50 micrograms a spray), 2 sprays each side everyday, using Balaam's design. Questionnaires, quality of life instruments, daily diary, Epworth Sleepiness Scale, and an overnight sleep test with polysomnograms were used as tools. The last 2 weeks of each 4-week treatment period were summarized, scored, and compared by PROC MIXED in SAS. Correlations between arousals on sleep tests and subjective tests were performed. Fluticasone improved subjective sleep when compared with placebo (p = 0.04); however, there was no difference in the apnea/hypopnea index in those that were treated. Daytime sleepiness and fatigue were decreased by > 10% in the treated group; however, this was not statistically significant. However, fluticasone used at approved doses improves subjective sleep in patients with perennial allergic rhinitis without a change in the apnea/hypopnea index.

Administration, Topical↗