The study was designed to assess the effect of cigarette smoking on the therapeutic response to oral corticosteroids in chronic stable asthma. We performed a randomized, placebo-controlled, crossover study with prednisolone (40 mg daily) or placebo for 2 weeks in smokers with asthma, ex-smokers with asthma, and never-smokers with asthma. All subjects had reversibility in FEV 1 after nebulized albuterol of 15% or more and a mean postbronchodilator FEV 1 % predicted of more than 80%. Efficacy was assessed using FEV 1 , daily PEF, and an asthma control score. There was a significant improvement after oral prednisolone compared with placebo in FEV 1 , ml (mean difference, 237; 95% confidence intervals, 43, 231; p ϭ 0.019), morning PEF L/m (mean difference, 36.8; 95% confidence intervals (CI), 11, 62; p ϭ 0.006), and asthma control score (mean difference, Ϫ0.72; 95% CI, Ϫ1.2, Ϫ0.3; p ϭ 0.004) in never-smokers with asthma but no change in smokers with asthma (mean differences of 47, 6.5, and Ϫ0.05 with p values of 0.605, 0.47, and 0.865, respectively). Ex-smokers with asthma had a significant improvement in morning and night PEF (mean difference, 29.1; CI, 2.3, 56; p ϭ 0.04 and 52.4; CI, 26, 79; p ϭ 0.003, respectively), but not in FEV 1 or asthma control score. We conclude that active smoking impairs the efficacy of short-term oral corticosteroid treatment in chronic asthma.Active cigarette smoking is common in adult patients with asthma, with over 20% being current smokers (1, 2). A recent survey of adults presenting to emergency departments with acute asthma revealed that 35% were cigarette smokers (3). Current smokers with asthma, compared with never-smokers, have more severe asthma symptoms (1, 2), an accelerated decline in lung function (4), an increase in hospitalization rates for asthma (5), and increased mortality after a near-fatal asthma attack (6). A further 22-43% of adults with asthma are ex-smokers (1, 2).There is relatively little information on the influence of cigarette smoking on the therapeutic effect of asthma medications. Corticosteroids are currently the best antiinflammatory therapy available for the treatment of asthma and are recommended in international guidelines (7). The evidence for these recommendations is based on clinical trials that have been undertaken largely in nonsmoking patients with asthma. In a randomized controlled trial, we recently found that active cigarette smoking impaired the efficacy of short-term inhaled corticosteroid treatment in steroid-naïve patients with asthma (8). This result confirmed an earlier uncontrolled study that reported a reduced response to inhaled corticosteroids in terms of airway function

In most developed countries y25% of adults with asthma are current cigarette smokers. Asthma and active cigarette smoking interact to cause more severe symptoms, accelerated decline in lung function, and impaired short-term therapeutic response to corticosteroids.Cigarette smoking may modify inflammation that is associated with asthma, although there is limited published data on airway pathology in smokers with asthma. To date, the evidence points towards a combination of both heightened and suppressed inflammatory responses in smokers compared with nonsmokers with asthma.The mechanisms of corticosteroid resistance in asthmatic smokers are unexplained, but could be as a result of alterations in airway inflammatory cell phenotypes (e.g. increased neutrophils or reduced eosinophils), changes in the glucocorticoid receptor-a to -b ratio (e.g. overexpression of glucocorticoid receptor b), and increased activation of pro-inflammatory transcription factors (e.g. nuclear factor-kB) or reduced histone deacetylase activity.In conclusion, every effort should be made to encourage asthmatics who smoke to stop, although the effects of smoking cessation upon reversing the adverse effects of tobacco smoke on asthma control, therapeutic response to corticosteroids and airway pathology have yet to be fully elucidated. Alternative or additional therapies to inhaled corticosteroids are needed for asthmatic patients who are unable to quit smoking.

By 6 wk after smoking cessation, subjects who quit smoking had achieved considerable improvement in lung function and a fall in sputum neutrophil count compared with subjects who continued to smoke. These findings highlight the importance of smoking cessation in asthma.

Introduction Irradiation of normal, non-malignant bone during cancer therapy can lead to atrophy and increased risk of fracture at several skeletal sites, particularly the hip. This bone loss has been largely attributed to damaged osteoblasts. Little attention has been given to increased bone resorption as a contributor to radiation-induced osteoporosis. Our aims were to identify if radiation increases bone resorption resulting in acute bone loss, and if bone loss could be prevented by administering risedronate. Methods Twenty-week old female C57BL/6 mice were either: not irradiated and treated with placebo (NR+PL); whole-body irradiated with 2 Gy X-rays and treated with placebo (IR+PL); or irradiated and treated with risedronate (IR+RIS; 30μg/kg every other day). Calcein injections were administered 7 and 2 days before sacrifice. Bones were collected 1, 2, and 3 weeks after exposure. MicroCT analysis was performed at 3 sites: proximal tibial metaphysis; distal femoral metaphysis; and the body of the 5th lumbar vertebra (L5). Osteoclasts were identified from TRAP-stained histological sections. Dynamic histomorphometry of cortical and trabecular bone was performed. Circulating TRAP5b and osteocalcin concentrations were quantified. Results In animals receiving IR+PL, significant (P < 0.05) reduction in trabecular volume fraction relative to non-irradiated controls was observed at all three skeletal sites and time points. Likewise, radiation-induced loss of connectivity and trabecular number relative to NR+PL were observed at all skeletal sites throughout the study. Bone loss primarily occurred during the first week post-exposure. Trabecular and endocortical bone formation was not reduced until Week 2. Loss of bone volume was absent in animals receiving IR+RIS. Histology indicated greater osteoclast numbers at Week 1 within IR+PL mice. Serum TRAP5b concentration was increased in IR+PL mice only at Week 1 compared to NR+PL (P = 0.05). Risedronate treatment prevented the radiation-induced increase in osteoclast number, surface, and TRAP5b. Conclusion This study demonstrated a rapid loss of trabecular bone at several skeletal sites after whole-body irradiation. Changes were accompanied by an increase in osteoclast number and serum markers of bone loss. Risedronate entirely prevented bone loss, providing further evidence that an increase in bone resorption likely caused this radiation-induced bone loss.

Cough severity and sputum ECP levels are modestly reduced by inhaled corticosteroids in patients with chronic cough persisting for more than 1 year. LTB(4), Cys-LT, PGE(2), IL-8, myeloperoxidase, and TNF-alpha levels are unaltered by this therapy. This raises the possibility that drugs targeted to reduce the effects of these mediators might be of benefit in chronic persistent cough.