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Biomedical subjects

Tom C Fardon

Publications and source records attributed to Tom C Fardon.

10 recordsLinked to original sources
PubMed2006

Respiratory symptoms, pulmonary function, and markers of inflammation among bar workers before and after a legislative ban on smoking in public places.

CONTEXT: Scotland prohibited smoking in confined public places on March 26, 2006. OBJECTIVE: To investigate the association of smoke-free legislation with symptoms, pulmonary function, and markers of inflammation of bar workers. DESIGN, SETTING, AND PARTICIPANTS: This prospective observational study was conducted in Tayside, Scotland from February-June 2006. One hundred five nonasthmatic and asthmatic nonsmoking bar workers were initially enrolled, of whom 77 completed the study per protocol. MAIN OUTCOME MEASURES: Respiratory and sensory symptoms, spirometry measurements, serum cotinine levels, peripheral inflammatory cell count, asthma quality-of-life scores, and exhaled nitric oxide levels were evaluated before and after introduction of the smoking ban. RESULTS: For the per-protocol analysis, the percentage of bar workers with respiratory and sensory symptoms decreased from 79.2% (n = 61) before the smoke-free policy to 53.2% (n = 41) (total change, -26%; 95% confidence interval [CI], -13.8% to -38.1%; P<.001) and 46.8% (n = 38) (-32.5%; 95% CI, -19.8% to -45.2%; P<.001) 1 and 2 months afterward. Forced expiratory volume in the first second increased from 96.6% predicted to 104.8% (change, 8.2%; 95% CI, 3.9% to 12.4%; P<.001) and then 101.7% (change, 5.1%; 95% CI, 2.1% to 8.0%; P = .002), and serum cotinine levels decreased from 5.15 ng/mL to 3.22 ng/mL (change, -1.93 ng/mL; 95% CI, -2.83 to -1.03 ng/mL; P<.001) and then 2.93 ng/mL (-2.22 ng/mL; 95% CI, -3.10 to -1.34 ng/mL; P<.001). The total white blood cell and neutrophil count was reduced from 7610 to 6980 cells/microL at 2 months (-630 cells/muL; 95% CI, -1010 to -260 cells/microL; P = .002) and from 4440 to 4030 cells/microL (-410 cells/microL; 95% CI, -740 to -90 cells/microL; P = .03), respectively. Asthmatic bar workers also had less airway inflammation, with a reduction in exhaled nitric oxide from 34.3 parts per billion (ppb) to 27.4 ppb 1 month after the ban (0.8-fold change; 95% CI, 0.67 to 0.96 ppb; P = .04), and Juniper quality-of-life scores increased from 80.2 to 87.5 points (7.3 points; 95% CI, 0.1 to 14.6 points; P = .049). CONCLUSIONS: Smoke-free legislation was associated with significant early improvements in symptoms, spirometry measurements, and systemic inflammation of bar workers. Asthmatic bar workers also had reduced airway inflammation and improved quality of life.

Adult↗
PubMed2006

A comparison of 2 extrafine hydrofluoroalkane-134a-beclomethasone formulations on methacholine hyperresponsiveness.

BACKGROUND: Small airways inflammation is a recognized pathologic component of asthma, and it is postulated that the observed airway-wall remodeling in small airways could be due to uncontrolled inflammation in airways that are not penetrated by conventional inhaled corticosteroids. Thus, extrafine particle formulations of inhaled corticosteroids are of clinical interest. OBJECTIVE: To compare 2 extrafine solution hydrofluoroalkane-134a formulations of beclomethasone dipropionate (Beclate and Qvar). METHODS: Fifteen asthmatic patients (mean +/- SEM forced expiratory volume in 1 second [FEV1], 2.62 +/- 0.21 L; provocative concentration of methacholine causing a 20% decrease in FEV1 [PC20], 1.06 +/- 0.58) were randomized to completion in a placebo-controlled, double-blind, crossover manner to receive Beclate or Qvar at doses of 100 or 400 microg/d for 2 weeks, with a 1-week washout period before each randomized treatment. Methacholine hyperresponsiveness was the primary outcome measure. RESULTS: The 2 formulations were equivalent in terms of predefined equivalence limits of +/- 1 doubling dilution for PC20 at both doses: -0.25 (95% confidence interval [CI], -0.77 to 0.27) doubling dilution difference between the 100-microg doses and a 0.26 (95% CI, -0.29 to 0.82) doubling dilution difference between the 400-microg doses for the difference between Beclate and Qvar, respectively. Both formulations, at either dose, produced a statistically significant (P < .05) reduction in mean exhaled nitric oxide levels: 400 microg/d of Beclate, 14.1 ppb (95% CI, 5.6 to 22.6 ppb); and 400 microg/d of Qvar, 14.2 ppb (95% CI, 6.0 to 22.4 ppb). The higher doses produced a statistically significant (P < .05) reduction in early morning urinary cortisol-creatinine ratio (geometric mean fold suppression: Beclate, 1.48 [95% CI, 1.16 to 1.89]; and Qvar, 1.42 [95% CI, 1.12 to 1.79]). Both formulations significantly improved peak expiratory flow, FEV1, and forced expiratory flow between 25% and 75% of forced vital capacity at the higher doses (P < .05). CONCLUSIONS: Beclate and Qvar were equivalent for all primary and secondary outcome measures.

Adolescent↗
PubMed2005

Addition of fexofenadine to inhaled corticosteroid therapy to reduce inflammatory biomarkers in atopic asthma.

BACKGROUND: We previously showed that H1-antihistamines may shift the PC20 (provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20%) threshold to adenosine monophosphate (AMP) challenge but may paradoxically prolong recovery. OBJECTIVES: To measure AMP recovery using a constant predetermined AMP PC20 and to evaluate whether fexofenadine use confers add-on effects to treatment with either fluticasone propionate alone or combined fluticasone propionate-salmeterol. METHODS: Fourteen atopic patients with mild-to-moderate asthma (forced expiratory volume in 1 second of 76%) completed a double-blind, randomized, crossover study consisting of 3-week treatment blocks of either fluticasone propionate-salmeterol, 250 microg twice daily, or fluticasone propionate alone, 250 microg twice daily, in conjunction with either fexofenadine, 180 mg once daily, or matched placebo. Recovery after a predetermined AMP PC20 challenge was measured (primary outcome), along with exhaled nitric oxide levels, plasma eosinophil cationic protein levels, peripheral eosinophil counts, pulmonary function, diary card outcomes, and quality of life (all secondary outcomes). RESULTS: There were no differences in any of the primary or secondary outcomes when fexofenadine was added to treatment with either fluticasone propionate-salmeterol or fluticasone propionate alone. The mean AMP recovery time was 25.0 vs 23.4 minutes for fexofenadine and placebo, respectively, as add-on to fluticasone-salmeterol and 22.5 vs 23.9 minutes, respectively, as add-on to fluticasone alone. CONCLUSION: Fexofenadine did not affect recovery to a fixed dose of AMP challenge or any other surrogate inflammatory markers when given as add-on therapy to corticosteroid-treatedatopic asthmatic patients.

Adenosine Monophosphate↗
PubMed2005

Evaluation of an abbreviated adenosine monophosphate bronchial challenge.

RATIONALE: Airway hyperresponsiveness to adenosine monophosphate (AMP) has been validated as a surrogate marker for airway inflammation. We wished to know whether an abbreviated challenge at the final threshold dose would produce the same fall in FEV1 as a full, conventional dose-response challenge. METHODS: Seventeen patients with mild-to-moderate asthma (mean FEV1, 75.5% predicted) attended for a full dose-response protocol, where the highest concentration of AMP to produce > 20% fall in FEV1 was noted, along with the maximum percentage fall and recovery time. Patients returned within 2 days for a further challenge, when they received only the highest concentration (as a single bolus) reached on the previous visit. RESULTS: The mean (+/- SEM) percentage fall in FEV1 after the full challenge was 25.5 +/- 1.3%, and after the abbreviated challenge was 9.4 +/- 2.4%. The mean recovery after the full challenge was 28.13 +/- 4.65 min, and after the abbreviated test was 10.81 +/- 4.27 min. CONCLUSION: An abbreviated challenge using a single bolus dose of AMP grossly underestimates bronchial hyperresponsiveness. Although the pharmacologic half-life of AMP is short (90 s), the lesser response and shortened recovery with the abbreviated challenge suggest a more prolonged physiologic half-life, which in turn may have implications for abbreviated challenge protocols.

Adenosine Monophosphate↗
PubMed2005

Decongestant effects of nasal xylometazoline and mometasone furoate in persistent allergic rhinitis.

Thirty-six persistent allergic rhinitis (PAR) sufferers were studied, to both compare and correlate 15 minute response to nasal xylometazoline (XYLO) with 28 day response to nasal mometasone furoate (MF). 0.1% XYLO (1 spray each nostril) response was measured on two occasions, then a randomised double blind cross-over comparison of MF (200 mcg daily) to placebo conducted. Outcomes were peak nasal inspiratoly flow (PNIF), nasal forced inspiratory volume in one second (nFIV1) and nasal blockage score (NBS) improvements. Thirty-one participants completed per protocol. Within subject standard deviation for percentage improvement to XYLO was 26.0 for PNIF and 25.2 for nFIV1. Median % improvement (95%CI) in PNIF for XYLO vs. MF was 20.0 (11.4 to 31.0) vs. 9.6 (3.2 to 15.8) and in nFIV1 was 17.8 (10.0 to 28.1) vs. 3.3 (-4.3 to 19.1). XYLO effects were greater than MF (p<0.05) for PNIF, nFIV1 and NBS. There was no significant correlation of MF to XYLO improvements in PNIF, nFIV1 or NBS. In conclusion, acute reversibility to XYLO showed poor repeatability and XYLO reversibility is not predictive of decongestant response to nasal corticosteroid. XYLO was a stronger decongestant than MF but rhinitis medicamentosa still precludes any preference for long term XYLO therapy at this time.

Administration, Intranasal↗
PubMed2004

Adrenal suppression with dry powder formulations of fluticasone propionate and mometasone furoate.

Mometasone furoate (MF) and fluticasone propionate (FP) are high potency inhaled corticosteroids. The systemic bioavailability of MF is claimed to be negligible, leading to a minimal potential for systemic adverse effects. We assessed the overnight urinary cortisol/creatinine as the primary outcome of adrenal suppression in 21 patients with persistent asthma (mean FEV1 = 91%). Patients were randomized in a crossover fashion to receive 2 weekly consecutive doubling incremental doses of either FP Accuhaler (500, 1,000, and 2,000 microg/day) or MF Twisthaler (400, 800, and 1,600 microg/day). For the 21 per protocol completed patients, there was significant suppression of overnight urinary cortisol/creatinine with high and medium doses of both drugs-as geometric mean fold suppression (95% confidence interval) from baseline: FP 2,000 microg, 1.85 (1.21-2.82, p = 0.002); FP 1,000 microg, 1.45 (1.07-1.96, p = 0.02); MF 1,600 microg, 1.92 (1.26-2.93, p = 0.001); and MF 800 microg, 1.39 (1.04-1.88, p = 0.02). For secondary outcomes of 8:00 A.M. plasma cortisol, serum osteocalcin, and early morning urinary cortisol/creatinine, there was significant suppression with MF and FP at the highest dose. Our data refute the assertion that MF has negligible systemic bioavailability and a lower potential for systemic adverse effects compared with FP.

Administration, Inhalation↗
PubMed2004

Comparative cutoff points for adenosine monophosphate and methacholine challenge testing.

BACKGROUND: Current use of the PC20 (provocation concentration that causes a decrease in forced expiratory volume in 1 second of 20%) cutoff point for bronchial challenge precludes its use in patients with more severe airflow obstruction. OBJECTIVE: To evaluate the efficacy and safety of lower cutoff points for adenosine monophosphate (AMP) and methacholine (MCH) bronchial challenge tools to monitor response to treatment in chronic asthma. METHODS: We retrospectively examined data from 5 previously published studies (2 using AMP, 2 using MCH, and 1 with MCH and AMP arms) and recalculated 10% and 15% cutoff points for AMP and MCH. Data were analyzed for correlation of single results and doubling dose shifts after anti-inflammatory treatment intervention. RESULTS: A total of 175 individual MCH challenges and 152 AMP challenges were evaluated. Evaluating the doubling dose shift produced by the addition of anti-inflammatory treatment (inhaled corticosteroids or montelukast) produced the following Pearson correlation coefficients: MCH PD20 (provocation dose that causes a decrease in forced expiratory volume in 1 second of 20%) vs PD15, 0.80; MCH PD20 vs PD10, 0.65; AMP PC20 vs PC15, 0.96; and AMP PC20 vs PC10, 0.84 (P < .001 for all). Subgroup analysis of AMP for before and after inhaled corticosteroids only (n = 41) shows AMP PC20 vs PC15 of 0.92 and AMP PC20 vs PC10 of 0.84 (P < .001 for both). CONCLUSIONS: The 10% and 15% cutoff points strongly predict the 20% cutoff value for AMP and MCH, as do the doubling dose shifts after anti-inflammatory treatment. The lower thresholds are suitable for monitoring response to therapy, and they expose patients to significantly less provocation agent.

Acetates↗