A trial of inhaled budesonide on airway responsiveness in smokers with chronic bronchitis. Effects of instruction by practice assistants on inhaler technique and respiratory symptoms of patients. A controlled randomized videotaped intervention study. An internet-based interactive telemonitoring system for improving childhood asthma outcomes in Taiwan. Efficacy and safety of oxitropium bromide, theophylline and their combination in COPD patients: a double-blind, randomized, multicentre study (BREATH Trial). A prospective evaluation of esophageal testing and a double-blind, randomized study of omeprazole in a diagnostic and therapeutic algorithm for chronic cough High-Dose N-Acetylcysteine in Patients with Exacerbations of Chronic Obstructive Pulmonary Disease Opiate therapy in chronic cough. Comparison of lidocaine and bronchodilator inhalation treatments for cough suppression in patients with chronic obstructive pulmonary disease Efficacy of speech pathology management for chronic cough: a randomised placebo controlled trial of treatment efficacy Influence of inhaled steroids on recovery from occupational asthma after cessation of exposure: an 18-month double-blind crossover study. Inhaled lodoxamide tromethamine in the treatment of perennial asthma: a double-blind placebo-controlled study. Evaluation of a mobile phone-based, advanced symptom management system (ASyMS©) in the management of chemotherapy-related toxicity Nonasthmatic chronic cough: No effect of treatment with an inhaled corticosteroid in patients without sputum eosinophilia. The National Mucolytic Study. Results of a randomized, double-blind, placebo-controlled study of iodinated glycerol in chronic obstructive bronchitis. Efficacy of HFA-beclomethasone dipropionate extra-fine aerosol (800 microg day(-1)) versus HFA-fluticasone propionate (1000 microg day(-1)) in patients with asthma. Effects of inhaled budesonide on spirometric values, reversibility, airway responsiveness, and cough threshold in smokers with chronic obstructive lung disease. Neltenexine tablets in smoking and non-smoking patients with COPD. A double-blind, randomised, controlled study versus placebo. AKL1, a botanical mixture for the treatment of asthma: a randomised, double-blind, placebo-controlled, cross-over study Efficacy of Supplemental Anti-Inflammatory Therapy with Fenspiride in Chronic Obstructive and Nonobstructive Bronchitis Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease Inhaled steroids improve quality of life in patients with steady-state bronchiectasis. Combined theophylline/beta-agonists maintenance therapy in chronic asthma. Effectiveness of montelukast in the treatment of cough variant asthma. Effects of the addition of nedocromil sodium to maintenance bronchodilator therapy in the management of chronic asthma. Nedocromil sodium versus theophylline in the treatment of reversible obstructive airway disease. A double-blind clinical trial of ketotifen and disodium cromoglycate in bronchial asthma. Effect of inhaled corticosteroids on symptom severity and sputum mediator levels in chronic persistent cough. N-acetylcysteine by metered dose inhaler in the treatment of chronic bronchitis: a multi-centre study. Formoterol for maintenance and as-needed treatment of chronic obstructive pulmonary disease. Protective effect of a bacterial extract against acute exacerbation in patients with chronic bronchitis accompanied by chronic obstructive pulmonary disease. A pathogenic triad in chronic cough: asthma, postnasal drip syndrome, and gastroesophageal reflux disease. High-dose inhaled beclomethasone treatment in patients with chronic cough: a randomized placebo-controlled study. Effect of codeine on objective measurement of cough in chronic obstructive pulmonary disease. Asthma symptoms and airway hyperresponsiveness are lower during treatment with nedocromil sodium than during treatment with regular inhaled albuterol. Antitussive Effect of the Leukotriene Receptor Antagonist Zafirlukast in Subjects with Cough-Variant Asthma* Loratadine in the treatment of cough associated with allergic rhinoconjunctivitis. Further studies on the clinical efficacy of Solanum xanthocarpum and Solanum trilobatum in bronchial asthma. Efficacy of Nebulized Flunisolide Combined with Salbutamol and Ipratropium Bromide in Stable Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease Equivalence of asthma control with new CFC-free formulation HFA-134a beclomethasone dipropionate and CFC-beclomethasone dipropionate. Proton pump inhibitor treatment of patients with gastroesophageal reflux-related chronic cough: a comparison between two different daily doses of lansoprazole. Effects of randomized assignment to a smoking cessation intervention and changes in smoking habits on respiratory symptoms in smokers with early chronic obstructive pulmonary disease: the Lung Health Study. Effects of imagery, critical thinking, and asthma education on symptoms and mood state in adult asthma patients: a pilot study. Treatment of chronic posterior laryngitis with esomeprazole. Antitussive activity of diphenhydramine in chronic cough Antitussive effects of the H1-receptor antagonist epinastine in patients with atopic cough (eosinophilic bronchitis). Evaluation of omeprazole in the treatment of reflux laryngitis: a prospective, placebo-controlled, randomized, double-blind study. Chronic non‐asthmatic cough is not affected by inhaled beclomethasone dipropionate Efficacy and Tolerability of Oral Acetylcysteine (Fabrol®) in Chronic Bronchitis: A Double-Blind Placebo Controlled Study Improving asthma control through telemedicine: a study of short-message service. Efficacy of Beclomethasone Dipropionate HFA 200 μg Once Daily in Chronic Obstructive Pulmonary Disease and Bronchial Asthma The use of twice daily nedocromil sodium in the treatment of asthma. Oral neltenexine in patients with obstructive airways diseases: an open, randomised, controlled comparison versus sobrerol. Effect of suplatast tosilate, a Th2 cytokine inhibitor, on cough variant asthma Comparison of Fenspiride with Beclomethasone as Adjunctive Anti-Inflammatory Treatment in Patients with Chronic Obstructive Pulmonary Disease The influence of ketotifen and aminophylline on the central and peripheral airways. A double-blind study of the efficacy of nedocromil sodium in the management of asthma in patients using high doses of bronchodilators. Prevalence of depressive symptoms among patients with chronic cough. Acute safety of beclomethasone dipropionate in a new CFC-free propellant system in asthmatic patients. Treatment of stable chronic bronchitis with iodinated glycerol: a double-blind, placebo-controlled trial.
The aim of the present r and omized , double-blind study was to evaluate the effect of inhaled budesonide on daily symptoms , ventilatory capacity , and airway responsiveness in smokers with chronic bronchitis . Twenty-five subjects with a provocative concentration producing a 20 % fall in forced expiratory volume in one second PC20(FEV1 ) less than 2.0 mg.ml-1 , by bronchial histamine challenge , were included . Eighteen subjects accomplished the entire 12 week study , eight receiving inhaled budesonide 400 micrograms b.i.d . and ten receiving placebo .  Cough decreased significantly in the actively treated group during the treatment period , but no change could be demonstrated in expectoration , dyspnoea , or sleep disturbances . No changes in any of these symptoms were found in the placebo group , and no differences in symptoms scores were found between the groups . No significant differences in ventilatory capacity or bronchial responsiveness could be demonstrated . In conclusion , a moderately high dose of inhaled steroid in eight subjects with chronic bronchitis did not improve the symptom scores , ventilatory capacity , or airway responsiveness to any clinical ly relevant degree BACKGROUND Many patients with asthma or chronic obstructive pulmonary disease use their medication inhalers incorrectly . General practitioners , pharmacists and other health care providers do not always have the opportunity to instruct patients in correct inhaler technique . OBJECTIVE To find out whether the inhaler technique and respiratory symptoms of patients can be improved after instruction by practice assistants . METHODS Single blind , r and omized intervention study in which 48 patients who had been using a dry powder inhaler for at least one month took part . Their inhaler technique was videotaped on two visits with a two-week interval between visits . The inhaler technique on the videos was subsequently scored by two experts on nine criteria . At both visits the patients completed a question naire about their respiratory symptoms . After the first video , 25 patients were r and omly chosen to receive instruction from one of six practice assistants who had followed a one evening course about inhaler instruction , and who had been issued an instruction-set . RESULTS The patients who received instruction had a significantly greater reduction in number of mistakes at the second visit than the patients who did not ( P = 0.01 ) . The instructed patients also reported less dyspnoea at the second visit ( P = 0.03 ) . No effect of instruction was found on wheezing , cough and sputum production . CONCLUSION The inhaler technique of patients can be improved significantly by the instruction of patients by trained practice assistants , possibly result ing in less dyspnoea A r and omized , controlled trial was conducted to assess the effectiveness of Blue Angel for Asthma Kids , an Internet-based interactive asthma educational and monitoring program , used in the management of asthmatic children . One hundred sixty-four ( n = 164 ) pediatric patients with persistent asthma were enrolled and r and omized into two study groups for a 12-week controlled trial . The intervention group had 88  participants who were taught to monitor their peak expiratory flows ( PEF ) and asthma symptoms daily on the Internet . They also received an interactive response consisting of a self-management plan from the Blue Angel monitoring program . The control group had 76 participants who received a traditional asthma care plan consisting of a written asthma diary supplemented with instructions for self-management . Disease control was assessed by weekly averaged PEF values , symptom scores , and asthma control tests . Adherence measures were assessed by therapeutic and diagnostic monitoring . Outcome was assessed by examining quality of life and retention of asthma knowledge . The data were analyzed by comparing results before and after the trial . At the end of trial , the intervention group decreased nighttime ( -0.08 + /- 0.33 vs. 0.00 + /- 0.20 , p = 0.028 ) and daytime symptoms ( -0.08 + /- 0.33 vs. 0.01 + /- 0.18 , p = 0.009 ) ; improved morning ( 241.9 + /- 81.4 vs. 223.1 + /- 55.5 , p = 0.017 ) and night PEF ( 255.6 + /- 86.7 vs. 232.5 + /- 55.3 , p = 0.010 ) ; increased adherence rates ( p < 0.05 ) ; improved well-controlled rates ( 70.4 % vs. 55.3 % , p < 0.05 ) ; improved knowledge regarding self-management ( 93.2 % vs. 70.3 % , p < 0.05 ) ; and improved quality of life ( 6.5 + /- 0.5 vs. 4.3 + /- 1.2 on a 7-point scale , p < 0.05 ) when compared with conventional management . The Internet-based asthma telemonitoring program increases selfmanagement skills , improves asthma outcomes , and appears to be an effective and well-accepted technology for the care of children with asthma and their caregivers We compare the efficacy including spirometry , peak expiratory flow ( PEFR ) and quality of life and safety of an 8-week treatment with inhaled oxitropium , theophylline or their combination in patients with mild-to-severe chronic obstructive pulmonary disease ( COPD ) . We conducted a multicentre , double-blind , double-dummy r and omized , parallel-group study at 29 Italian out patients clinics . A group of 236 patients with mild-to-severe COPD ( baseline FEV1 < or = 70 % of predicted value ) were recruited . Treatments were as follows : Inhaled oxitropium bromide 200 microg ( N=75 ) , sustained-release oral theophylline 300 mg ( N=81 ) or their combination ( N=80 ) , taken twice daily .  Spirometry ( FEV1 and FVC ) was evaluated every 4 weeks , and morning and evening PEFR ( before and 2 - 4 h after drug intake ) was measured daily . Symptoms , cough and dysponea , were recorded daily . Health status was evaluated at baseline and week 8 using the disease specific St George ' Respiratory Question naire ( SGRQ ) . Any adverse event occurring during the treatment period was recorded on a diary card . FEV1 and FVC improved in all the groups at 4 and 8 weeks , but the difference between treatment groups did not reach statistically significant levels . Differences between groups in pre-dosing morning and evening PEFR were not significant . Post-dosing morning and evening PEFR were increased and the largest increase was seen in patients treated with both drugs . However , differences between groups was significant only for evening values ( P=0.008 ) . The proportion of patients who experienced a decrease in symptoms was high in all groups but no differences among groups were observed . SGRQ total scores decreased in all treatment groups after 8 weeks , particularly in the oxitropium and combination groups . Clinical ly significant change ( > or = 4 units ) was only observed in patients treated with oxitropium bromide whether with or without theophylline .  Adverse events related to treatments were higher in the group treated with theophylline alone ( P < 0.02 ) . We conclude that inhaled oxitropium bromide alone was associated with an improvement in FEV1 , PEFR and symptoms in patients with COPD that was not statistically different from that of oral theophylline alone or of the combination of both drugs . Oxitropium bromide in combination with theophylline provided a greater improvement in evening post-dosing PEFR . Oxitropium bromide alone or in combination with theophylline improved the quality of life better than theophylline alone Objective : Recent studies suggest an association between chronic cough and gastroesophageal reflux . Our study aims were 1 ) to define the prevalence of acid reflux induced cough in the general community , 2 ) to examine the ability of esophageal testing to identify gastroesophageal reflux related cough , and 3 ) to assess the utility of omeprazole in a chronic cough algorithm . Methods : Patients with chronic cough of unknown etiology , who were mostly from the community , were evaluated . Subjects underwent a chest x-ray , methacholine challenge test , and empiric trial of postnasal drip therapy , and completed daily cough symptom diaries subjectively evaluating cough frequency and severity on a grade d scale of 0–4 ( combined maximum 8) . After excluding other causes of cough , the remaining patients underwent esophageal and pH testing . Those testing positive were r and omized to omeprazole 40 mg b.i.d . or placebo for 12 weeks . Follow-up was 1 yr . Results : A total of 71 patients were screened ; 48 were excluded . Twenty-three patients were evaluated for gastroesophageal reflux disease ; six ( 26 % ) were eventually determined to have an acid-related cough . Of these patients , 17 had a positive pH test , six ( 35 % ) of whom showed a striking improvement or resolution of their cough during omeprazole treatment which was sustained for up to 1 yr . Six had a negative pH test , none of whom responded to omeprazole therapy . No significant differences were seen between responders ( n = 6 ) and nonresponders ( n = 11 ) for demographic factors , baseline symptom frequency and duration , or physiological parameters ( motility/pH ) . Conclusions : Acid-related chronic cough was present in 26 % ( six of 23 ) of patients evaluated for gastroesophageal reflux disease . Esophageal testing does not reliably identify patients with acid induced chronic cough responsive to proton pump inhibitor therapy . We suggest that the best diagnostic and therapeutic approach , after excluding asthma and postnasal drip syndrome , is empiric treatment for 2 wk with a high dose proton pump inhibitor Abstract Objective : To investigate the efficacy and tolerability of high-dose N-acetylcysteine ( NAC ) in the treatment of patients with exacerbations of chronic obstructive pulmonary disease ( COPD ) . Design and patients : R and omised , double-blind , double-dummy , placebo-controlled study in 123 patients experiencing an acute exacerbation of COPD . Interventions : NAC 1200 mg/day , 600 mg/day or placebo administered once daily for 10 days . Main outcome measures : The primary objective was to assess the proportion of patients with normalised C-reactive protein ( CRP ) levels . Also assessed were effects on interleukin (IL)-8 levels , lung function and symptoms . Results : Both NAC 600 and 1200 mg/day were associated with a significantly higher proportion of patients achieving normalised CRP levels compared with placebo ( 52 % and 90 % vs 19 % of patients ; p ≤ 0.01 ) ; however , NAC 1200 mg/day was superior to NAC 600 mg/day ( p = 0.002 ) . Furthermore , treatment with NAC 1200 mg/day was more efficacious than NAC 600 mg/day in reducing IL-8 levels and difficulty of expectoration , while the two active regimens had similar beneficial effects on lung function and other clinical outcomes ( cough intensity and frequency , and lung auscultation ) . Treatments were well tolerated with one adverse event reported in NAC 1200 mg/day recipients and two reported in placebo recipients . Conclusion : Treatment with NAC 1200 mg/day improved biological markers and clinical outcomes in patients with COPD exacerbations . It is speculated that the effect of NAC on inflammatory markers may be due to both mucolytic and antioxidant properties RATIONALE Cough is the most common complaint for which medical attention is sought , and chronic cough can be both physically and mentally debilitating . There is currently no evidence supporting the use of antitussives in chronic treatment-resistant cough . OBJECTIVES We tested the hypothesis that morphine sulfate in the dose of 5 mg twice daily would bring about a reduction in cough frequency and severity in patients failing to respond to specific measures . METHODS Patients recruited from the Hull Cough Clinic were enrolled into a r and omized double-blind placebo-controlled study using 4 weeks of slow-release morphine sulfate and a corresponding period of matched placebo . An open-labeled extension of the core study allowed dose escalation to 10 mg twice daily . Cough was assessed using the Leicester Cough Question naire , daily symptom diary , and citric acid cough challenge . RESULTS Twenty-seven patients completed the core study . A significant improvement of 3.2 points over baseline was noted on the Leicester Cough Question naire ( p < 0.01 ) . A rapid and highly significant reduction by 40 % in daily cough scores was noted among patients on slow-release morphine sulfate ( p < 0.01 ) . Objective testing of the cough reflex using citric acid cough challenge tests did not show any significant changes . Eighteen patients continued into the extension study . Two-thirds of these patients opted to increase the morphine to 10 mg twice daily . At the end of 3 months , there was a similar improvement in cough between the 5- and 10-mg groups . CONCLUSION Morphine sulfate is an effective antitussive in intractable chronic cough at the doses of 5 to 10 mg twice daily Background : This study aim ed to assess and compare the effectiveness of lidocaine and bronchodilator inhalation treatments for rapid cough suppression in patients with chronic obstructive pulmonary disease ( COPD ) . Methods : Prospect i ve comparison study carried out in a tertiary emergency department . Consecutive COPD patients presenting with intractable cough were r and omly assigned to receive lidocaine or terbutaline inhalation treatments for cough suppression . Patients with dyspnoea , unstable vital signs , and pneumonia or neoplasm on chest x ray were excluded . A subjective , 10 point question naire based cough severity score was used for assessing the outcome . Results : The final study sample included 127 patients ( mean ( SD ) age , 69.2 ( 12.1 ) years ; 33.1 % women ) of whom 62 received nebulised lidocaine and 65 nebulised bronchodilator . The cough severity score was significantly reduced one hour after inhalation treatment with both lidocaine and bronchodilator , with no significant difference in efficacy . Common but mild side effects in the lidocaine group included oropharyngeal numbness and bitter taste , and , in the bronchodilator group , tremor and palpitation . Dyspnoea , dizziness , and nausea and vomiting were equally uncommon in both groups . None of these problems caused any of the patients to discontinue their treatments and no allergic reactions were reported . Conclusions : Both lidocaine and bronchodilator inhalation treatments are equally effective for short term cough suppression in patients with COPD Background : Chronic cough that persists despite medical treatment may respond to speech pathology intervention , but the efficacy of such treatment has not been investigated in prospect i ve r and omised trials . The aim of this study was to determine the efficacy of a speech pathology intervention programme for chronic cough . Methods : A single blind , r and omised , placebo controlled trial was conducted in 87 patients with chronic cough that persisted despite medical treatment . Patients were r and omly allocated to receive either a specifically design ed speech pathology intervention or a placebo intervention . Participants in both groups attended four intervention sessions with a qualified speech pathologist . Results : Participants in the treatment group had a significant reduction in cough ( 8.9 to 4.6 , p<0.001 ) , breathing ( 7.9 to 4.7 , p<0.001 ) , voice ( 7.3 to 4.6 , p<0.001 ) upper airway ( 8.9 to 5.9 , p<0.001 ) symptom scores and limitation ( 2.3 to 1.6 , p<0.001 ) ratings following intervention . There was also a significant reduction in breathing ( 6.8 to 5.6 , p = 0.047 ) , cough ( 7.6 to 6.3 , p = 0.014 ) , and limitation ( 2.3 to 2.0 , p = 0.038 ) scores in the placebo group , but the degree of improvement was significantly less than in the treatment group ( p<0.01 ) . Clinical judgement of outcome indicated successful ratings in 88 % of participants in the treatment group compared with 14 % in the placebo group ( p<0.001 ) . Conclusion : Speech pathology is an effective management intervention for chronic cough which may be a viable alternative for patients who do not respond to medical treatment Occupational asthma ( OA ) is a useful model for the study of asthma in humans . The possibility that inhaled corticosteroids , in addition to withdrawal from the workplace , could improve clinical and functional recovery from OA can be hypothesized . We assessed clinical , functional , and behavioral characteristics of 32 subjects ( 22 male , 10 female ) , in all but one of whom OA was confirmed by specific inhalation challenges induced by either high- ( n=13 ) or low-molecular-weight ( n=19 ) agents within 3 mo after cessation of exposure . In this r and omized , crossover , double-blind study , subjects ( paired for baseline PC20 and duration of symptoms after exposure ) received either placebo or 1,000 micrograms of inhaled beclomethasone daily for 1 yr , followed by the alternate medication for 6 mo . Various clinical , functional , and behavioral parameters were examined at each 3-mo visit . Significant improvement in clinical ( nocturnal symptoms , cough ) , functional ( morning and evening peak expiratory flow rates ) , and behavioral ( quality of life ) parameters were detected in the active-treatment period , although the magnitude of the improvement was relatively small . Side effects ( oropharyngeal , reduced cortisol ) were similar in the placebo and treatment groups . Distinguishing subjects who started with the active preparation from those who were given placebo first showed that most clinical and behavioral parameters improved in the former instance , whereas there was no significant difference in the latter . We conclude that inhaled corticosteroids induce a small but significant overall improvement of the  asthmatic condition in subjects with occupational asthma caused by high- and low-molecular-weight agents after withdrawal from exposure . The beneficial effect is , however , more pronounced if inhaled steroids are given early after diagnosis The efficacy of lodoxamide tromethamine in the treatment of asthma was studied in a 16-week double-blind , placebo-controlled study of 68 perennial allergic subjects with asthma . Patients received either lodoxamide tromethamine , 0.25 mg four times daily , or placebo , administered by metered-dose inhaler . Response to treatment was assessed by analyzing changes in asthma symptoms , inhaled bronchodilator requirements , and pulmonary function when compared to a 2-week baseline period . Patients treated with lodoxamide tromethamine demonstrated an improvement in daytime breathing difficulty , cough , sputum production , and sleep ( p less than 0.01 to 0.05 ) , but improvement was not significantly different from that demonstrated by placebo-treated patients . Patients from both treatment groups were able to reduce their inhaled bronchodilators ( p less than 0.01 ) , but again no significant difference was apparent between lodoxamide tromethamine and placebo treatment , nor were there any differences in peak expiratory flow rate or FEV1 between the two groups . Seven patients who received lodoxamide tromethamine withdrew because of a sensation of heat and gastrointestinal symptoms . Thus , although lodoxamide tromethamine possesses potent mast cell-stabilizing activity in vitro , we have failed to demonstrate any useful long-term effect in the treatment of mild allergic asthma Objectives To evaluate the impact of a mobile phone-based , remote monitoring , advanced symptom management system ( ASyMS © ) on the incidence , severity and distress of six chemotherapy-related symptoms ( nausea , vomiting , fatigue , mucositis , h and –foot syndrome and diarrhoea ) in patients with lung , breast or colorectal cancer . Design A two group ( intervention and control ) by five time points ( baseline , pre-cycle 2 , pre-cycle 3 , pre-cycle 4 and pre-cycle 5 ) r and omised controlled trial . Setting Seven clinical sites in the UK ; five specialist cancer centres and two local district hospitals . Participants One hundred and twelve people with breast , lung or colorectal cancer receiving outpatient chemotherapy . Interventions A mobile phone-based , remote monitoring , advanced symptom management system (ASyMS © ).Main outcome measures Chemotherapy-related morbidity of six common chemotherapy-related symptoms ( nausea , vomiting , fatigue , mucositis , h and –foot syndrome and diarrhoea ) . Results There were significantly higher reports of fatigue in the control group compared to the intervention group ( odds ratio = 2.29 , 95%CI = 1.04 to 5.05 , P = 0.040 ) and reports of h and –foot syndrome were on average lower in the control group ( odds ratio control/intervention = 0.39 , 95%CI = 0.17 to 0.92 , P = 0.031 ) . Conclusion The study demonstrates that ASyMS © can support the management of symptoms in patients with lung , breast and colorectal cancer receiving chemotherapy BACKGROUND Inhaled corticosteroids are effective in suppressing a  chronic cough  without asthma associated with sputum eosinophilia . OBJECTIVE To investigate the inflammatory characteristics in the induced sputum of patients with a chronic cough without asthma or known cause and the effects of budesonide treatment on chronic cough in those patients . PATIENTS AND METHODS Forty-four adults ( mean [ minimu , maximum ] age of 45 years [ 20,75 ] , 28 women , 17 atopic subjects and 32 nonsmokers ] , with a daily bothersome cough for at least one year and who had no evidence of asthma or other known cause for the cough , were consecutively enrolled . The trial was a r and omized , double-blind , controlled parallel group trial of budesonide 400 mg twice daily for two weeks versus placebo . Patients then received open administration of the same dose of budesonide for a further two weeks . Sputum was induced before and at the end of each treatment period . Cough severity was documented by a visual analogue scale . RESULTS Thirty-nine ( 89 % ) patients produced mucoid sputum after induction on at least one study visit . At baseline , the majority ( 59 % ) had a mild elevation in the median proportion of neutrophils ( 65 % ) . All had elevated fluid phase levels of fibrinogen ( 3200 mg/L ) and albumin ( 880 mg/L ) , and high levels of interleukin-8 and substance P. Interleukin-8 correlated with neutrophils ( rho=0.72 , P<0.001 ) , fibrinogen ( rho=0.65 , P<0.001 ) , albumin ( rho=0.67 , P=0 . 001 ) and eosinophil cationic protein ( rho=0.60 , P=0.001 ) . Substance P correlated with albumin ( rho=0.60 , P=0.006 ) . No subject had an increase in eosinophils . Treatment with budesonide did not affect cough or sputum measurements . CONCLUSIONS Patients with nonasthmatic chronic cough enrolled in this study had evidence of a mild neutrophilia and /or microvascular leakage . Chronic cough did not respond to treatment with budesonide , perhaps because the cause was not associated with sputum eosinophilia Seventy-four pulmonologists and one allergist were recruited to assess the efficacy and safety of iodinated glycerol ( Organidin ) , 60 mg qid , vs placebo in patients with stable chronic obstructive bronchitis in a r and omized , double-blind , placebo-controlled , parallel design . A total of 361 patients ( 180 to iodinated glycerol and 181 to placebo ) who complained of cough and difficulty bringing up sputum entered the eight-week study . Evaluations were based upon eight primary symptom efficacy parameters ( cough frequency , cough severity , chest discomfort , dyspnea , ease in bringing up sputum , patient and physician global assessment s , and a derived patients ' global assessment ) , and six secondary parameters ( frequency of aerosol bronchodilator use , incidence and duration of acute exacerbations , frequency of concomitant medication use , incidences of adverse experiences and dropouts ) . Cough frequency , cough severity , chest discomfort , patients ' ease in bringing up sputum , patients ' overall condition , and a derived subject global assessment were significantly ( p less than 0.05 ) improved by iodinated glycerol as compared with placebo within eight weeks of treatment . Dyspnea showed a trend toward improvement and the physicians ' global evaluation showed no significant difference between groups . Similar findings were noted in a subgroup analysis of moderately-to-severely affected patients . The mean duration ( days ) of acute exacerbations and number of dropouts attributable to adverse experiences were significantly less ( p less than 0.05 ) in the iodinated glycerol group . ( ABSTRACT TRUNCATED AT 250 WORDS Hydrofluoroalkane-134a beclomethasone dipropionate ( HFA-BDP ) extra-fine aerosol and HFA-fluticasone propionate ( HFA-FP ) are chlorofluorocarbon-free inhalers . We conducted an 8-week , open study to demonstrate the equivalence of HFA-BDP ( 800 microg day(-1 ) ) and HFA-FP ( 1000 microg day(-1 ) ) in moderate to severe asthma . Symptomatic patients on 500 - 1000 microg day(-1 ) CFC-BDP ( or equivalent ) and short-acting beta-agonist , were r and omized to HFA-BDP ( n = 101 ) or HFA-FP ( n = 97 ) after 7 - 14 ( + /-2 ) day run-in . In the intent-to-treat ( ITT ) population ( n = 198 ) , both treatments provided clinical ly and statistically significant improvements in asthma control , with increases in peak expiratory flow in the morning ( AM PEF ) and asthma symptoms ( within treatment analysis P<0.05 ) . Mean ( SE ) change in AM PEF from baseline at week 8 was equivalent ( defined as 90 % CI for the mean difference between treatments within + /-25 l min(-1 ) ) in the two groups : 29.59 ( 5.19 ) l min(-1 ) for HFA-BDP vs. 17.3 ( 5.45 ) l min(-1 ) for HFA-FP ( 90 % CI-0.02 , 24.91 ) . For the per protocol population ( n = 121 ) , the mean ( SE ) change in AM PEF from baseline was not equivalent ; AM PEF improved to a significantly greater extent in the HFA-BDP group than HFA-FP group [ 34.84 ( 7.08 ) vs. 20.63 ( 7.32 ) l min(-1 ) P<0.01 ; 90 % CI ; 2.66 , 31.10 ] . At week 8 in the ITT population , there were no statistically significant differences in FEV1 , beta-agonist use , asthma symptom/sleep disturbance scores , or percentage of days without asthma symptoms/sleep disturbance . There was a significantly greater reduction from baseline in mean eosinophil count for  HFA-BDP  compared with HFA-FP at weeks 3 and 8 ( P<0.01 ) , and eosinophil cationic protein value at week 8 ( P<0.01 ) . Both treatments were well tolerated and there were no statistically significant differences in urinary cortisol creatinine parameters . In conclusion , this study showed that , in patients with moderate-to-severe symptomatic asthma , HFA-BDP extra-fine aerosol 800 microg(-1 ) was at least as effective and equally well tolerated as 1000 microg day(-1 ) HFA-FP Inhaled corticosteroids are known to reduce respiratory symptoms and airway responsiveness in allergic patients with asthma . The aim of the present r and omised , double blind study was to assess the effect of eight weeks ' treatment with inhaled budesonide in non-allergic smokers with chronic obstructive lung disease . Twenty four subjects ( 23 male ) entered the study . Their ages ranged from 40 to 70 ( mean 57 ) years , with a mean of 35 ( range 9 - 80 ) pack years of smoking ; the mean FEV1 was 53 % ( range 32 - 74 % ) predicted and geometric mean PC20 ( histamine concentration causing a 20 % fall in FEV1 ) 0.96 ( range 0.07 - 7.82 ) mg/ml . After a two week washout , single blind , placebo period , 12 patients were allocated to treatment with budesonide 1600 microgram/day and 12 to placebo for eight weeks . The only additional drug to be taken was ipratropium bromide " if needed . " Twenty one patients completed the study , 10 in the budesonide group and 11 in the placebo group . The st and ard deviation of the difference between duplicate measurements of PC20 histamine and citric acid cough threshold made two weeks apart was below one doubling dose step . There was a significant reduction in dyspnoea in the budesonide group , but otherwise no change in symptom scores or use of ipratropium bromide over the eight weeks of treatment within or between the two groups . No significant differences in spirometric values , peak expiratory flow , PC20 histamine , or citric acid cough threshold were found between the groups . Although differences were not significant , some of the changes showed a trend in favour of budesonide . Whether a longer observation period would show a significant influence of inhaled corticosteroids in patients with chronic obstructive lung disease remains to be determined BACKGROUND The aim of this double-blind , r and omised , controlled study vs placebo was to evaluate the efficacy and tolerability of neltenexine ( tablets ) versus placebo ( tablets ) , administered to smoking and non-smoking patients with chronic obstructive pulmonary disease ( COPD ) . METHODS Sixty patients with mild stable COPD were recruited . The exclusion criteria were lung cancer , pulmonary tuberculosis , asthma , cystic fibrosis , bronchiectasis , community-acquired pneumonia ( CAP ) , intercurrent infections , concomitant treatment with corticosteroids , antitussives , beta2 agonists , anticholinergic and other mucolytic agents . The patients were allocated r and omly to receive neltenexine ( 20 smokers and 20 non-smokers ) or a matching placebo ( 20 smokers ) , 1 tablet twice daily for 20 days . The efficacy criteria were sputum characteristics and volume , difficulty in expectorating , cough , dyspnoea , pulmonary auscultation , forced expiratory volume in one second ( FEV1 ) , vital capacity and arterial partial oxygen pressure ( PO2 ) . Tolerability was monitored and adverse events were reported . RESULTS At the study end , the improvement of patients treated with  neltenexine  ( smokers and non-smokers ) was greater and statistically significant as compared with the patients in the placebo group in terms of improvement of dyspnoea ( p<0.02 ) , cough ( p<0.02 ) , pulmonary auscultation ( p<0.02 ) , and difficulty in expectorating ( p<0.02 ) . Furthermore , a significant improvement of the sputum characteristics ( p<0.02 ) and volume ( p<0.01 ) was evidence d , as compared with patients treated with placebo , in non smoking patients treated with neltenexine and in smoking patients treated with neltenexine . CONCLUSIONS The study confirmed earlier clinical experiences showing that neltenexine is effective in the treatment of COPD patients and highlighted the correlation between abstention from smoking and the efficacy of mucoactive treatment Background Despite effective treatments , asthma outcomes remain suboptimal . Interest exists in complementary therapies , particularly in herbal remedies for asthma treatment , currently with inconclusive evidence of efficacy . The encapsulated botanical mixture AKL1 has anecdotal evidence of effectiveness in asthma . Methods We performed a r and omised controlled cross over study comparing the effectiveness of AKL1 with indistinguishable placebo as add-on therapy in patients uncontrolled on st and ard asthma treatment . Thirty two adult asthmatics completed a 36 week trial consisting of a 4 week single blind run in period , during which placebo was added to usual treatment , a 12 week double blind active phase in which subjects received AKL1 or placebo , a single blind 8 week washout period receiving placebo and a final 12 week double blind cross-over active treatment phase . Daily diaries were kept of peak expiratory flow and symptoms , and spirometry , vali date d symptom and health status question naire scores and adverse events were monitored at study visits . Paired T tests were used to compare the effects of placebo and AKL1 on outcomes . Changes in outcome measures over treatment phases are presented as means and 95 % confidence intervals ( CI ) of means . Results No significant differences in lung function ( active-placebo ) were found ( Forced Expiratory Volume in 1 second : mean difference [ 95 % CI ] = 0.01 [ -0.12 to 0.14 ] L , p = 0.9 . Peak Expiratory Flow : -4.08 [ -35.03 to 26.89 ] . L/min , p = 0.8).Trends to clinical improvements favouring active treatment were however consistently seen in the patient-centered outcomes : Asthma Control Question naire mean difference ( active – placebo ) [ 95 % CI ] = -0.35 [ -0.78 to 0.07 ] , p = 0.10 , Asthma Quality of Life Question naire mean difference 0.42 [ -0.08 to 0.93 ] , p = 0.09 , Leicester Cough Question naire mean difference 0.49 , [ -0.18 to 1.16 ] , p = 0.15.Nine exacerbations occurred during placebo treatment and five whilst on AKL1 . No significant adverse events were noted . Conclusion AKL1 treatment was well tolerated . No significant improvements in lung function , symptoms , or quality of life were seen , although consistent trends were seen to improvements in patient-centered outcomes . Further studies are needed Abstract Objective : The objective of this r and omised , nonblind study was to assess the efficacy of fenspiride as complementary anti-inflammatory therapy in combination with ipratropium bromide in patients with chronic bronchitis ( CB ) . A comparison was made with ipratropium bromide alone , the generally accepted st and ard therapy for CB . Methods and subjects : The study population comprised 20 patients with chronic obstructive bronchitis ( COB ) and 60 patients without signs of obstruction . Fifty-one males ( 64 % ) and 29 females ( 36 % ) aged from 25 to 65 years were studied over a 6-month treatment period . Combined therapy with fenspiride ( 160 mg/day ) and ipratropium bromide ( 160 μg/day ) was prescribed to 39 patients ( 28 with CB and 11 with COB ) for 6 months , and monotherapy with ipratropium bromide ( 160 μg/day ) was prescribed for 41 patients ( 32 with CB and nine with COB ) . Results : The combined therapy group had a reduced intensity of dyspnoea , improvements in sputum nature and quantity of exudation , and a reduced intensity of coughing . The monotherapy group showed reductions in sputum exudation and cough intensity . Improvements in lung respiratory function were observed in both groups , but were greater in the combined therapy group of patients . Reduced cytosis , percentage and absolute content of neutrophils , and absolute content of lymphocytes and eosinophils in induced sputum were observed with CB patients in the combined therapy group . A reduced content of lymphocytes and an increase in macrophages were observed with CB patients in the monotherapy group . A significant decline in tumour necrosis factor (TNF)-α content in sputum was observed with both therapeutic regimens , although a statistically significant decline in serum TNFα ( 10.85 ng/L to 5.58 ng/L ; p = 0.03 ) and reduced interleukin-8 in sputum ( 311.94 ng/L to 122.02 ng/L ; p = 0.027 ) were observed with patients given combined therapy . Conclusion : The study showed greater efficacy of long-term treatment with fenspiride and ipratropium bromide compared with ipratropium bromide alone in patients with CB . This combination regimen can be recommended for the reduction of inflammation and prevention of disease progression in patients with CB and may also be useful in patients with COB BACKGROUND The efficacy of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease ( COPD ) remains controversial because of a lack of placebo-controlled studies . We compared the effect of inhaled fluticasone propionate with placebo in the treatment of patients with COPD . METHODS We used a r and omised , double-blind , placebo-controlled design . We enrolled from 13 European countries , New Zeal and , and South Africa , 281 outpatient current or ex-smokers , aged between 50 and 75 years . They had a forced expiratory volume in 1 s ( FEV1 ) of between 35 % and 90 % of predicted normal values , a ratio of FEV1 to forced vital capacity of 70 % or less and bronchodilator reversibility of less than 15 % , as well as a history of chronic bronchitis . Patients were r and omly assigned fluticasone propionate 500 microg ( n=142 ) or placebo ( n=139 ) twice daily via a metered-dose inhaler for 6 months . The main outcome measures were the number of patients who had at least one exacerbation by the end of treatment , the number and severity of exacerbations , clinic lung function , diary card symptoms and peak expiratory flow and 6 min walking distance . FINDINGS 51 ( 37 % ) patients in the placebo group compared with 45 ( 32 % ) in the fluticasone propionate group had had at least one exacerbation by the end of treatment ( p=0.449 ) . Significantly more patients had moderate or severe exacerbations in the placebo group than in the fluticasone propionate group ( 86 % vs 60 % , p<0.001 ) . Diary-card and clinic morning peak expiratory flows improved significantly in the fluticasone propionate group ( p<0.001 , p=0.048 , respectively ) , as did clinic FEV1 ( p<0.001 ) , forced vital capacity ( p<0.001 ) , and mid-expiratory flow ( p=0.01 ) . Symptom scores for median daily cough and sputum volume were significantly lower with fluticasone propionate treatment than with placebo ( p=0.004 and p=0.016 , respectively ) . At the end of treatment , patients on fluticasone propionate had increased their 6 min walking distance significantly more than those on placebo ( p=0.032 ) . Fluticasone propionate was tolerated as well as placebo , with few adverse effects and without a clinical ly important effect on mean serum cortisol concentration . INTERPRETATION Fluticasone propionate may be of clinical benefit in patients with COPD over at least 6 months .  Inhaled corticosteroids may have an important role in the long-term treatment of COPD BACKGROUND The effects of inhaled steroids upon the quality of life of patients with bronchiectasis remain unknown . STUDY OBJECTIVE To analyze the effect of inhaled fluticasone propionate ( FP ) for 6 months upon the clinical , functional , microbiological and outcome parameters of patients with steady-state bronchiectasis not due to cystic fibrosis , and its repercussions for patient health-related quality of life ( HRQoL ) . DESIGN Prospect i ve , r and omized , double-blind ( for effective doses ) study . PATIENTS AND INTERVENTIONS The diagnosis of bronchiectasis was made by high-resolution computed tomography . Ninety-three patients ( mean age : 68.5 [ 8.4 ] ) were r and omized to receive 250 microg bid , 500 microg bid or no treatment with inhaled FP for 6 months . Data were collected at baseline and at 1 , 3 and 6 months after the start of treatment . HRQoL was assessed using the vali date d Spanish version of the St. George 's Respiratory Question naire . RESULTS The group administered FP 1000 microg daily showed significant improvement in dyspnea ( 1.03 [2.1]-1.24 [ 2.2 ] points ; P = 0.01 - 0.04 ) , sputum production ( P = 0.001 ) , days without cough ( P = 0.02 ) and short-acting beta-2 agonists used ( P = 0.01 ) from the first month of treatment , with no changes in pulmonary function , number or severity of exacerbations , or microbiological profile of the sputum . As a result , an improvement in HRQoL was seen in this group after 3 months of treatment ( 45.4 [ 14.2 ] vs. 40.5 [ 13.9 ] ; P = 0.01 ) . CONCLUSIONS Inhalatory FP 500 microg bid is effective from the first month of treatment for controlling the symptoms of patients with steady-state bronchiectasis-thus ensuring a significant improvement in The therapeutic value of adding a slow-release theophylline product ( Theo-Dur ) to the regular treatment program consisting of beta-stimulants and steroids was evaluated in 31 adult asthmatics .  Theophylline in a dose of 300 mg or placebo was administered twice daily during two 14-day periods in a r and omized double-blind cross-over study . PEF and asthma symptoms were recorded daily . In the morning , 12 h after tablet intake ,  spirometry  was performed and the theophylline concentration determined . The addition of theophylline slightly , but statistically significantly , increased the daily PEF values and reduced dyspnoea , but not cough , sputum volumes and aerosol consumption . The patients showed preference for the combined treatment . Spirometry at the end of each period did not differ significantly between treatments . The mean theophylline concentration in the morning 12 h after tablet intake was 39 mumol/l ( range 15 - 81 mumol/l ) . The results of the study suggest that the addition of a slow-release theophylline preparation to beta-stimulant therapy provides further relief of asthma symptoms without an unacceptable increase in the incidence of side-effects BACKGROUND Antileukotriene agents have been shown to be beneficial in chronic asthma . Although patients with cough variant asthma have cough with minimal wheezing and dyspnea , airway hyperresponsiveness from chronic inflammation is believed to be the underlying mechanism . OBJECTIVE To evaluate the effectiveness of montelukast , a leukotriene receptor antagonist , in the treatment of cough variant asthma . METHODS Fourteen patients with cough variant asthma participated in a r and omized , double-blind , placebo-controlled trial with a 7- to 10-day baseline period and a 4-week treatment period with montelukast , 10 mg , or placebo daily . Inclusion criteria were ( 1 ) chronic cough with a duration of at least 4 weeks with minimal or no wheezing or dyspnea and ( 2 ) forced expiratory volume in 1 second of 50 % to 85 % of predicted and reversibility of 12 % with use of an inhaled beta-agonist or forced expiratory volume in 1 second greater than 85 % and positive methacholine challenge results . Patients fulfilled the minimum criteria for cough frequency and symptom scores for r and omization . RESULTS Eight patients received montelukast and 6 received placebo . The primary efficacy variable , mean percentage change from baseline in cough frequency , was significantly improved by the second week , and by the fourth week the mean percentage change from baseline was 75.7 % for the treatment group and 20.7 % for the placebo group . CONCLUSIONS The leukotriene receptor antagonist montelukast seems to be effective in the treatment of cough variant asthma . Larger studies are recommended to confirm this effect STUDY OBJECTIVES To assess the efficacy and safety of nedocromil sodium metered dose aerosol as an adjunct to sustained-released theophylline therapy in adult theophylline-dependent asthma patients and to examine the ability of nedocromil sodium to substitute for theophylline . DESIGN R and omized double-blind placebo-controlled parallel group study . Two-week baseline , eight-week treatment period . SETTING Out-Patient Clinic . PATIENTS Sequential sample of 35 adult chronic asthmatic patients maintained on a regimen of sustained-release theophylline ( dose range , 400 to 800 mg daily ) and on-dem and inhaled beta 2-bronchodilators . All patients completed the study . INTERVENTIONS 2 x 2-mg nedocromil sodium metered dose aerosol twice daily or matching placebo r and omly allocated after two-week baseline . Theophylline dose reduced by half or one third after four weeks of test treatments , then stopped for final two weeks . Use of inhaled beta 2-bronchodilators permitted throughout trial period . MEASUREMENTS AND RESULTS The following results were in favor ( statistically significant findings , p less than 0.05 ) of nedocromil sodium compared with placebo : all diary card efficacy variables ( nighttime asthma , morning tightness , daytime asthma , cough , twice daily peak expiratory flow [ PEF ] , inhaled beta 2 use ) during all periods of assessment ( weeks 1 to 2 , 3 to 4 , 5 to 6 , and 7 to 8) with the exception of cough and nighttime beta 2 use during weeks 1 to 2 ; patient and clinician opinion of treatment efficacy ( end of weeks 4 and 8) ; ability to reduce the theophylline dose ; clinician assessment of asthma severity at the end of the study , and clinic FEV1 at weeks 4 , 5 , 6 , and 8 . One placebo-treated patient reported transient moderately severe nausea and taste loss . No clinical ly significant changes were seen in the laboratory data . CONCLUSION Nedocromil sodium , 4 mg twice daily , conferred significant benefit when added to sustained-release theophylline therapy . The results suggest that nedocromil sodium may permit a reduction in theophylline dosage and possibly substitute for theophylline in previously dependent patients BACKGROUND Previous clinical therapeutic research has shown that inhaled nedocromil sodium can replace maintenance oral sustained release theophylline in the management of asthma patients . OBJECTIVE To compare directly the efficacy and safety of nedocromil sodium and sustained release theophylline . METHODS Using a r and omized , double-blind , double-dummy , parallel-group design , 105 patients with reversible obstructive airways disease ( 77 asthmatic patients ) recruited from four referred-care clinics received , in addition to their existing therapy , 4 mg nedocromil sodium four times daily or sustained release theophylline ( maximum daily dose 13 mg/kg ) for 6 weeks . Patients with serum theophylline levels within the therapeutic range of 10 to 20 micrograms/mL were retained for efficacy analysis . All were included in a tolerability analysis . Day and nighttime symptoms , inhaled bronchodilator use , morning tightness , cough , and twice daily peak flows were recorded on diary cards . Disease severity , lung function and unusual events were evaluated bi-weekly , and opinion of treatment after 6 weeks . RESULTS Both treatments improved symptoms , inhaled bronchodilator use and lung function to the same extent . Both treatments were very to moderately effective in > 70 % patients . The occurrence of gastrointestinal ( P < .05 ) and central nervous system ( P < .01 ) unusual events was significantly lower for nedocromil sodium compared with theophylline treated patients . CONCLUSIONS Nedocromil sodium and theophylline were equally effective in this group of patients but nedocromil sodium treatment was associated with significantly fewer side effects , and therefore may be the treatment of choice A double-blind cross-over trial compared the efficacy of  ketotifen ( 1 mg b.d . ) and DSCG  ( 20 mg q.d.s . ) as prophylactic therapy for asthma . It involved two eight-week periods of active therapy , each being preceded by two weeks of double placebo treatment . Analysis of symptoms recorded on diary cards showed that there was a reduction in the cough score in the atopic asthmatics on DSCG compared to ketotifen , and reductions in the cough score , wheeze and dyspnoea on DSCG when compared with placebo . There was a significant reduction in the diurnal variation in PEFR during treatment with DSCG compared to ketotifen and improvement in morning PEFR on DSCG compared with placebo . It was concluded that DSCG result ed in a significant therapeutic effect during the trial , whereas ketotifen ( 1 mg b.d . ) did not BACKGROUND Chronic cough often lasts for more than 1 year and is associated with airway inflammation . The effect of inhaled corticosteroids on symptom severity and inflammatory mediator levels in these patients is unknown . OBJECTIVE We sought to determine whether inhaled corticosteroids reduce cough severity and sputum mediator concentrations in patients with chronic persistent cough . METHODS We performed a double-blind , r and omized , placebo-controlled crossover study with inhaled fluticasone , 500 microg twice daily , and placebo for 14 days in 88 patients with cough for more than 1 year , with normal chest radiography and spirometry results . Outcome measures were a daily cough visual analogue scale and induced sputum concentrations of eosinophilic cationic protein ( ECP ) , myeloperoxidase , leukotriene B(4 ) ( LTB(4 ) ) , leukotrienes C(4)/D(4)/E(4 ) ( cysteinyl leukotrienes [ Cys-LTs ] ) , prostagl and in E(2 ) ( PGE(2 ) ) , IL-8 , and TNF-alpha . Sputum cell counts , exhaled nitric oxide levels , and carbon monoxide levels were also measured . RESULTS There was a significant improvement in the cough visual analogue scale after inhaled fluticasone compared with placebo ( mean difference , 1.0 ; 95 % CI , 0.4 - 1.5 ; P < .001 ) . LTB(4 ) , Cys-LT , and PGE(2 ) levels were increased in all causes of cough . Sputum ECP counts , exhaled nitric oxide levels , and carbon monoxide levels decreased significantly after inhaled fluticasone . There was no change in sputum cell counts and other mediator concentrations . CONCLUSION 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 Sixty-five patients with chronic bronchitis were studied at five different centres in a double-blind , r and omized trial . Two parallel groups were treated with either N-acetylcysteine or placebo by metered dose inhalers for 16 weeks . Following a 1-week run-in period , each patient recorded subjective impressions of the drug action on their bronchitic symptoms in a diary once a week . In addition , exacerbations were registered . Lung function testing and adverse effects were evaluated by four visits to the chest clinics during the 16 weeks . We could not demonstrate that N-acetylcysteine by metered dose inhalers had any significant effect on patients ' feeling of well-being , sensation of dyspnoea , intensity of coughing , mucus production , or expectoration or lung function . Its effect in reducing exacerbations could not be estimated because of a very low number of exacerbations reported . N-acetylcysteine inhalation was safe when used over a 16-week period Formoterol is a long-acting beta2-agonist with a rapid onset of effect in patients with chronic obstructive pulmonary disease ( COPD ) , making it potentially suitable for both maintenance and as-needed bronchodilator treatment . To evaluate the efficacy and tolerability of maintenance formoterol in patients with COPD and to compare the effects of additional formoterol as needed with terbutaline . In this 6-month , double-blind study , 657 patients with COPD ( 40 years , forced expiratory volume in 1s [ FEV1 ] 40 - 70 % predicted normal ) were r and omized to formoterol 9 microg twice daily ( bid ) plus terbutaline 0.5 mg as needed ( FORM bid ) , formoterol 9 microg bid plus formoterol 4.5 microg as needed ( FORM bid+prn ) , or placebo bid plus terbutaline 0.5 mg as needed ( placebo ) , all administered via Turbuhaler . Primary efficacy variables were FEV1 and the sum of breathlessness and chest tightness scores combined symptom score . Formoterol significantly ( P<0.01 ) increased FEV(1 ) compared with placebo : FORM bid 6.5 % ( 95 % CI : 2.5 , 10.7 % ) ; FORM bid+prn 11.8 % ( 95 % CI : 7.7 , 16.2 % ) . Combined symptom score decreased significantly in both formoterol groups compared with placebo : FORM bid -0.27 ( 95 % CI : -0.49 , -0.06 ; P=0.012 ) ; FORM bid+prn -0.32 ( 95 % CI : -0.53 , -0.11 ; P=0.0026 ) . Similar significant ( P<0.05 ) improvements were seen in both formoterol groups for morning peak expiratory flow , cough and sleep scores , and reliever use . In this study , formoterol 9 microg bid via Turbuhaler as maintenance therapy , with either formoterol or terbutaline as rescue medication , provided sustained improvements in lung function and COPD symptoms . Both formoterol regimens were well tolerated with no differences in adverse events or electrocardiogram profiles BACKGROUND Immunostimulating agents made from bacterial extracts represent a class of medications that contains antigens derived from several bacterial strains and their potential ability to prevent bacterial infections results from the stimulation of the nonspecific component of the immune system . The present study investigated the effect of the oral immunostimulant Broncho-Vaxom , which includes material from eight different species of bacteria that are frequently present in the lower respiratory tract , on the frequency and severity of acute exacerbation in patients with chronic bronchitis accompanied by chronic obstructive pulmonary disease ( COPD ) . METHODS Ninety patients with chronic bronchitis complicated with COPD were r and omly divided into groups A and B. Forty-nine subjects in group A received oral capsules containing 7 mg Broncho-Vaxom , while 41 patients in group B received similar placebo capsules . Both groups took one capsule daily for the first 10 days of each month for 3 consecutive months . The frequency of acute exacerbation , symptom scores , and lung function were recorded for the following one year period . RESULTS There was a significant decrease in the incidence , duration , and severity of acute exacerbation , as well as a reduction in the course of antibiotics administered and in the dosage of bronchodilator and mucolytic agent in group A , as compared to group B ( P < 0.05 , respectively ) . Symptom scores for cough , sputum , dyspnea , as well as symptoms observed upon auscultation of the chest also improved significantly in group A as compared to group B ( P < 0.05 , respectively ) . The bacterial clearance rate in sputum cultures from patients who received no antibiotics for the first 3 months was also significantly higher in group A compared to group B ( P < 0.01 ) . CONCLUSIONS Orally administered Broncho-Vaxom is associated with a decrease in the incidence of acute exacerbation and a decrease in the need for antibiotics and symptomatic relief medications in patients with chronic bronchitis accompanied by COPD . Broncho-Vaxom is also associated with a decrease in symptom scores . Without causing any apparent adverse effects , this drug may also help to eradicate pathogenic bacteria in the airways BACKGROUND Coughing may be produced by a number of different disorders in distinct anatomic sites . Chronic cough causes major functional limitation in a considerable patient population and requires careful evaluation . METHODS Seventy-eight nonsmoking patients of both genders who complained of cough for > or =3 weeks and had normal findings on plain chest radiographs were studied prospect ively . Their histories were obtained , and physical examinations were performed . The diagnostic workup included pulmonary function tests , CT of the paranasal sinuses and chest , carbachol provocation test , fiberoptic rhinoscopy , fiberoptic bronchoscopy , and 24-h esophageal pH monitoring . The final diagnosis depended on clinical , radiologic , and laboratory findings ; a successful response to therapy was required for confirmation . RESULTS The causes of chronic cough were determined in all patients .  Coughing was due to a single cause in 30 patients ( 38.5 % ) and multiple causes in 48 patients ( 61.5 % ) . The five most important causative factors were asthma ( 46 patients ; 58.9 % ) , postnasal drip syndrome ( PNDS ; 45 patients ; 57.6 % ) , gastroesophageal reflux disease ( GERD ; 32 patients ; 41.1 % ) , bronchiectasis ( 14 patients ; 17.9 % ) , and tracheobronchial collapse ( 11 patients ; 14.1 % ) . INTERPRETATION Asthma , PNDS , and GERD , alone or in combination , were responsible for 93.6 % of the cases of chronic cough . The presence of these three conditions was so frequent that the expression " pathogenic triad of chronic cough " should be acknowledged in specialized literature . It is essential to consider pulmonary and extrapulmonary causes in order to prescribe a successful specific therapy for chronic cough BACKGROUND It is important to determine whether chronic cough is associated with asthma and can be helped by treatment with inhaled corticosteroids . OBJECTIVE To compare the effects of beclomethasone and placebo in patients with chronic cough for at least 8 weeks after excluding those with cough due to postnasal drip and gastroesophageal reflux disease . METHODS A prospect i ve , r and omized , double-blind , placebo-controlled study comprising 64 patients was performed for 2 weeks . The active group received metered-dose inhaler chlorofluorocarbon-beclomethasone ( 1,500 microg/d ) , and the placebo group received identical-appearing placebo inhalers . All the participants completed a respiratory question naire and underwent bronchoprovocation testing ( BPT ) with methacholine and allergy skin testing . The primary outcome measure was a decrease in daily cough scores ( symptom diary and visual analog scale ) during the 2-week treatment period . RESULTS The active group comprised 44 patients and the placebo group 20 patients .  Cough duration averaged 20 weeks . At the end of treatment 82 % of the active group and 15 % of the placebo group had complete resolution of cough . In the active group 22 patients ( 50 % ) had positive BPT results , and in the placebo group 10 patients ( 50 % ) had positive results . There was no correlation between treatment response and responses on the respiratory question naire , allergy skin testing , or BPT . CONCLUSION Therapy with high-dose inhaled beclomethasone provided an excellent response in a subgroup of patients with chronic cough that did not correlate with atopy or airway hyperresponsiveness BACKGROUND Codeine is the st and ard antitussive treatment to which novel agents are compared . Little is known about the objective effect of any treatments on cough in chronic obstructive pulmonary disease ( COPD ) . OBJECTIVE To quantify the effect of codeine on objective cough frequency ( quantified as time spent coughing : cough seconds , cs/h ) , citric acid cough threshold , and subjective measures in a double-blind , placebo-controlled crossover study in COPD . METHODS We studied 21 patients with physician-diagnosed , stable disease who complained of cough ( 76.9 % male ; mean age , 67.7 years ; mean predicted FEV(1 ) , 53.4 % ; median smoking history , 43.5 pack-years ) . Each subject performed a cough challenge ( single breath , citric acid ) , 10-hour daytime ambulatory and overnight cough recordings , subjective cough scores , and visual analog scales at baseline and on 2 study days , 1 week apart . Codeine phosphate 60 mg or matched placebo were given , in r and om order , at the start of each cough recording ( 0 and 12 hours ) . RESULTS Median time spent coughing at baseline was 8.27 cs/h ( interquartile range [ IQR ] , 5.94 - 11.67 ) ; after placebo treatment , 7.22 cs/h ( IQR 4.42 - 10.40 ) ; and after codeine treatment , 6.41 cs/h ( IQR 3.86 - 9.10 ) . Codeine treatment had a significant effect on time spent coughing compared with baseline ( P = .02 ) but not compared with placebo ( P = .52 ) . There were no significant differences in cough challenge thresholds ( log concentration of tussive agent causing 2 coughs or log concentration of tussive agent causing 5 coughs ) or subjective cough measures for codeine compared with placebo . CONCLUSION In this study , codeine was no more effective than placebo in patients with COPD complaining of cough . CLINICAL IMPLICATION S Codeine is the antitussive agent to which we compare new treatments ; however , in a group of stable patients with COPD , it had no effect on cough frequency over placebo In a double-blind , double-dummy , multicenter study , 212 patients with asthma whose symptoms were not controlled by as-needed use of inhaled bronchodilators were r and omized to receive either 4 mg of nedocromil sodium or 180 micrograms of albuterol four times daily for 12 weeks . Asthma symptom scores ( daytime asthma , nighttime asthma , morning chest tightness , and cough ) and peak expiratory flow rate were recorded daily on diary cards . Bronchial hyperresponsiveness was assessed by changes in diurnal variation in peak expiratory flow rate and by methacholine inhalation challenge . Statistically significant differences were found between groups favoring nedocromil sodium for relief of day and nighttime asthma and morning chest tightness . Patients treated with nedocromil sodium also had significantly lower diurnal variation in peak expiratory flow rate compared with patients treated with albuterol . Compared with patients treated with albuterol , patients treated with nedocromil sodium showed a greater improvement in cough and a decreased sensitivity to methacholine challenge . Patients in both groups reduced their as-needed albuterol use . Regular treatment with nedocromil sodium therefore led to greater asthma symptom control and reduced bronchial responsiveness compared with regular treatment with albuterol . The study also showed that more frequent use of a beta 2-agonist ( for symptom relief or not ) did not improve asthma control . Both drugs were well tolerated Cough-variant asthma ( CVA ) occurs in a subgroup of asthmatics whose sole or predominant respiratory symptom is cough . Although bronchodilators are often sufficient to treat CVA , refractory cough may require therapy with inhaled or systemic corticosteroids . In a r and omized , double-blind , placebo-controlled , crossover study , we examined the effect of a 14-day course of the leukotriene receptor antagonist zafirlukast on subjective cough score and cough-reflex sensitivity to inhaled capsaicin in eight subjects with CVA refractory to inhaled beta agonists , and in five subjects refractory to inhaled corticosteroids . Seven of eight subjects experienced significant subjective and objective improvement in cough after treatment with zafirlukast . Mean ( ± SEM ) cough score improved from 7.75 ± 0.56 to 3.25 ± 0.84 ( p = 0.0006 ) . Cough sensitivity to capsaicin was suppressed by zafirlukast in all subjects . Patients with CVA may represent a distinct subgroup of asthmatics whose afferent cough receptors within the respiratory epithelium are hypersensitive relative to those of patients with the typical form of asthma . Zafirlukast appears to be particularly effective in treating CVA by inhibiting the sensitivity of these receptors . Leukotriene receptor antagonists may offer an alternative to corticosteroids for the treatment of CVA refractory to inhaled bronchodilators BACKGROUND Antihistaminic treatment of allergic asthma or cough-type asthma , including cough associated with allergic rhinocojunctivitis , has been recently reconsidered prospect ively since new very potent compounds , nonsedating with anti-allergic properties , are available . OBJECTIVE The possible effectiveness of loratadine in the treatment of allergic cough was assessed in 20 patients with allergic rhinoconjunctivitis and cough due to Parietaria judaica during the pollen season ( April to July 1993 ) . METHODS Allergic patients were enrolled in a double-blind , placebo-controlled , parallel-group , r and omized study , and received loratadine 10 mg/d or placebo in oral tablets for 4 weeks . Occurrence and severity of conjunctival and nasal symptoms , severity and frequency of cough attacks were assessed daily by the patients together with peak expiratory flow evaluation performed twice a day , ie , in the morning and in the evening . Physicians evaluated conjunctival and nasal signs , and spirometry on admission ( before treatment ) , 2 and 4 weeks after treatment . On admission methacholine challenge was also performed to assess PD20 . Pollen counts were assessed during the study . RESULTS According to patients ' diary cards , ocular and nasal symptoms were progressively reduced by loratadine treatment ( respectively P < .05 and P < .01 ) , as well as cough frequency ( P < .05 ) and cough intensity ( P < .01 ) . Peak expiratory flow rate , forced vital capacity , and forced expiratory volume in one second significantly decreased in the placebo-treated group ( P < .01 ) , while they were not modified in loratadine-treated patients , who remained normal . CONCLUSIONS The study suggests that loratadine may be beneficial in the treatment of allergic cough , as well as in rhinoconjunctivitis . Further studies of this may be warranted The clinical efficacy of two herbs S. xanthocarpum and S. trilobatum in a dose of 300 mg tds for 3 days was investigated in mild to moderate bronchial asthma . Their effect was compared with st and ard bronchodilator drugs , salbutamol ( 4 mg ) and deriphylline ( 200 mg ) . The respiratory function was assessed by measuring the peak expiratory flow rate ( PEFR ) using a mini peak flow meter . In addition , improvement in lung function was assessed by physical examination ( rhonchi and crepitation ) and other symptoms such as cough , breathlessness and sputum .  S. xanthocarpum and S. trilobatum produced a progressive improvement in the ventilatory function of asthmatic individuals over 3 days . The scores for rhonchi , cough , breathlessness and sputum were decreased by these drug treatments . The improvement in PEFR and the reduction in other symptom scores clearly indicate a bronchodilator effect , a decrease of oedema and secretions in the airway lumen . The response to these herbs can be considered to be equivalent to that of deriphylline but less than salbutamol . No untoward effects were reported during the study . The present study further confirms the traditional use of these herbs in bronchial asthma Background : The efficacy of nebulized corticosteroids in the prevention of exacerbation of chronic obstructive pulmonary disease ( COPD ) has been poorly studied . Objective : To evaluate the efficacy and tolerability of nebulized flunisolide ( 1 mg ) + salbutamol/ipratropium bromide ( 1,875/375 µg ) b.i.d . in comparison with placebo + salbutamol/ipratropium bromide . Methods : This was a r and omized , parallel-group , double-blind study on 114 patients with COPD of moderate-to-severe degree . The main outcome was the frequency of severe exacerbations over a 6-month period . Before and after treatment , respiratory symptoms , forced expiratory volume in 1 s ( FEV1 ) , shuttle walking test distance and St. George ’s Respiratory Question naire scores were evaluated . Results : The total number of exacerbations was slightly lower in the flunisolide group compared to the placebo group ( 19 vs. 34 , p = 0.054 ) ; the number of patients experiencing at least one exacerbation during the study was also decreased ( 16 vs. 26 , p = 0.059 ) . In particular , type 3 Anthonisens ’s exacerbations were significantly reduced by flunisolide ( p = 0.044 ) . In the placebo group , scores were higher than in the flunisolide group but nonsignificant for dyspnea , cough , sputum amount and purulence . FEV1 was significantly increased compared to baseline in both groups , and the area under the FEV1-time curve during the 6-month period was significantly greater in the flunisolide group ( 5.2 ± 10.6 vs. 2.1 ± 5.0 , flunisolide vs. placebo , respectively ; p = 0.047 ) . For shuttle walking test distance and scores of the St. George ’s Respiratory Question naire , no significant difference between the baseline evaluation and the end of the study was observed in both groups . Conclusions : Nebulized flunisolide is a good alternative to other inhaled corticosteroids when added to nebulized salbutamol/ipratropium bromide in the long-term treatment of moderate-to-severe COPD patients The study was design ed to test for equivalence of asthma control between a new aerosol formulation of beclomethasone dipropionate ( BDP ) incorporating a chlorofluorocarbon-(CFC ) free , hydrofluoroalkane propellant ( HFA-134a ) and the conventional beclomethasone aerosol formulated in CFC propellants .  Sixty-eight asthmatic patients entered an eight-week , r and omised , double-blind crossover study . All patients , previously stabilised on BDP , were r and omised to receive the same dose of BDP from each of the study treatments . Statistically significant equivalence was demonstrated between HFA-BDP and CFC-BDP for asthma control parameters : FEV1 , morning and evening PEF , sleep disturbance , wheeze and cough , morning breathlessness and bronchodilator use . Such equivalence was also demonstrated for safety parameters . To conclude , it has been demonstrated that HFA-BDP achieves a level of asthma control that is clinical ly and statistically equivalent to CFC-BDP in terms of efficacy and safety , at total daily doses ranging from 200 micrograms to 600 micrograms in asthma patients previously stabilised on inhaled CFC-BDP AIM To compare two different daily doses of lansoprazole given for 12 weeks and to assess the role of gastrointestinal ( GI ) investigations as criteria for selecting patients . METHODS Out of 45 patients referred for unexplained chronic persistent cough , 36 had at least one of the GI investigations ( endoscopy , 24-h esophageal pH-metry and a 4-week trial of proton pump inhibitor ( PPI ) therapy ) positive and were r and omly assigned to receive either 30 mg lansoprazole o.d . or 30 mg lansoprazole b.i.d . for 12 weeks . Symptoms were evaluated at baseline ( visit 1 ) after the PPI test ( visit 2 ) and after the 12-week lansoprazole treatment period ( visit 3 ) . RESULTS Thirty-five patients completed the study protocol . Twenty-one patients ( 60.0 % ) reported complete relief from their cough with no difference between the two treatment groups ( 58.8 % and 61.1 % had no cough in 30 mg lansoprazole and 60 mg lansoprazole groups , respectively ) . More than 80 % of the patients who had complete relief from their cough at the end of the treatment showed a positive response to the PPI test . CONCLUSION Twelve weeks of lansoprazole treatment even at a st and ard daily dose , is effective in patients with chronic persistent cough . A positive response to an initial PPI test seems to be the best criterion for selecting patients who respond to therapy PURPOSE To evaluate the effects of r and omly assigning smokers who have early chronic obstructive pulmonary disease ( COPD ) to a smoking-cessation intervention on the symptoms of chronic cough , chronic phlegm production , wheezing and shortness of breath , and to determine the effects of quitting smoking on these symptoms . SUBJECTS AND METHODS A total of 5,887 male and female smokers 35 to 60 years of age with early COPD [ defined as a forced expiratory volume in the first second ( FEV1 ) of 55 % to 90 % of predicted and FEV1/forced vital capacity ( FVC ) < 0.70 ] were enrolled in a 5-year clinical trial . Two-thirds of participants were r and omly assigned to  smoking-intervention groups  and one-third to a usual-care group . The intervention groups attended 12 intensive smoking-cessation sessions that included behavior modification techniques and the use of nicotine chewing gum . One intervention group was treated with ipratropium bromide by inhaler ; the other intervention group received placebo inhalers . The usual-care group was advised to stop smoking . All participants were followed annually . Smoking status was biochemically vali date d by salivary cotinine measurements or exhaled carbon monoxide values . RESULTS Vali date d 5-year sustained smoking cessation occurred in 22 % of participants in the intervention compared with only 5 % of participants in the usual-care group . At the end of the study , the prevalence of each of the four symptoms in the two intervention groups was significantly less than in the usual-care group ( P < 0.0001 ) . For example , among participants who did not report cough at baseline , 15 % of those in the intervention groups had cough at least 3 months during the year , compared with 23 % of those in usual care . Sustained quitters had the lowest prevalence of all four symptoms , whereas continuous smokers had the greatest prevalence of these symptoms . Changes in symptoms occurred primarily in the first year after smoking cessation . Respiratory symptoms were associated with greater declines in FEV1 during the study ( P < 0.001 ) . Ipratropium bromide had no long-term effects on respiratory symptoms . CONCLUSIONS In this prospect i ve r and omized trial using an intention-to-treat analysis , smokers with early COPD who were assigned to a smoking-cessation intervention had fewer respiratory symptoms after 5 years of follow-up OBJECTIVE To compare biologically targeted imagery ( BTI ) and critical thinking asthma management ( CTAM ) outcomes . DESIGN Participants were r and omized to BTI ( group 1 , G1 ) or CTAM ( group 2 , G2 ) in a 2 x 2 x 4 design ( BTI/CTAM x pretest/post-test x weeks [ 3 week averaged intervals of symptoms and peak flows ] ) . Interventions were asthma education plus treatment ( BTI or CTAM for two 2-hour sessions per week for 6 weeks ) . For BTI , data collection ( symptoms , lung function ) occurred preintervention ( 3 week baseline ) , during the intervention ( 6 weeks ) , and postintervention ( 6 weeks ) . For CTAM , data collection occurred at wait-list control ( WLC ) ( 12 weeks extended baseline ) , preintervention ( 3 weeks ) , during the intervention ( 6 weeks ) , and postintervention ( 6 weeks ) . SETTING Alaska Regional Hospital , Anchorage . SUBJECTS Seventy ( 70 ) adults ( 53 women , 17 men ) with asthma . INTERVENTIONS WLC record keeping , BTI , or CTAM . OUTCOME MEASURES Dependent variables included asthma symptoms ( wheezing , coughing , sleep , activity , attacks , peak flow ) and self-report assessment s of Profiles of Mood States ( POMS-BI ) ( anxiety , hostility , depression , uncertainty , fatigue , confusion ) ; Knowledge , Attitude , and Self-Efficacy Asthma Question naire ( KASE-AQ ) ; Health Attribution Test ( HAT ) for locus of control ( LoC ) ; and the Revised Asthma Problem Behavior Checklist ( RAPBC ) . RESULTS Analyses of covariance with repeated measures contrasted BTI pre- to post-tests , time periods , and WLC ; CTAM pre- to post-tests , time periods , and extended baseline WLC ; and BTI to CTAM outcomes . WLC improved all POMS-BI scores except anxiety , increased internal LoC , and reduced problematic behaviors . Compared to WLC , BTI reduced wheezing , anxiety , and chance LoC , and increased asthma knowledge , attitude , and self-efficacy . Compared to CTAM , BTI reduced wheezing and chance LoC , increased internal LoC , and improved 6 POMS-BI scores . Compared to extended baseline WLC , CTAM increased asthma knowledge , attitude , self-efficacy , internal LoC , and peak flow . CONCLUSIONS Both interventions significantly improved symptoms and asthma management more than record keeping . Contrary to hypothesis , BTI produced better outcomes than CTAM OBJECTIVE To evaluate the efficacy of acid-suppressive therapy with the proton pump inhibitor esomeprazole on the signs and symptoms of chronic posterior laryngitis ( CPL ) in patients with suspected reflux laryngitis . STUDY DESIGN Prospect i ve , multicenter , r and omized , parallel-group trial that compared twice-daily esomeprazole 40 mg with placebo for 16 weeks . METHODS Eligible patients had a history of one or more CPL symptoms ( throat clearing , cough , globus , sore throat , or hoarseness ) and laryngoscopic signs indicating reflux laryngitis based on CPL index ( CPLI ) scores measured during a screening laryngoscopy . Patients were r and omized to treatment if their 7-day screening diary-card recordings showed a cumulative primary symptom score of 9 or higher and they had 3 or more days with moderately severe symptoms based on a 7-point scale . Efficacy was assessed by changes in symptoms as recorded by patients and investigators and by changes in CPLI scores based on laryngoscopic examinations . RESULTS The patients ' primary CPL symptom at final visit ( primary efficacy end point ) was resolved in 14.7 % ( 14/95 ) and 16.0 % ( 8/50 ) of patients in the esomeprazole and placebo groups , respectively ( P=.799 ) . Esomeprazole and placebo were not significantly different for change from baseline to the final visit in mean total CPLI ( -1.66+/-2.13 vs. -2.0+/-2.55 , respectively ; P=.446 ) or any other secondary efficacy end points based on patient diary card or investigator assessment s. CONCLUSION This study provides no evidence of a therapeutic benefit of treatment with esomeprazole 40 mg twice daily for 16 weeks compared with placebo for signs and symptoms associated with CPL A double‐blind crossover study was conducted to evaluate the antitussive effectiveness of diphenhydramine ( DPH ) in  chronic coughs related to bronchitis , at doses of25 and 50 mg every 4 hr for four doses . Both 25− and 50‐mg doses caused a statistically and clinical ly significant reduction in frequency of coughs , compared to placebo . The most frequently reported side effect was drowsiness , principally at the 50‐mg dose level . There was little or no apparent correlation between antitussive effectiveness and incidence of drowsiness , however , suggesting that the two effects were pharmacologically unrelated Chronic cough is the only symptom of eosinophilic bronchitis ( EB ) . There is considerable overlap between EB and atopic cough . To investigate the antitussive effects of a histamine H1-recetor antagonist , epinastine hydrochloride ( epinastine , CAS 80012 - 43 - 7 , Alesion ; 20 mg/day , once daily ) , cough scores , pulmonary function , capsaicin cough threshold , and bronchial hyperresonsiveness ( BHR ) to methacholine ( MCh ) were evaluated before and after a 4-week treatment with epinastine in patients with EB . In the epinastine group , the cough scores were decreased significantly ( 18.3 + /- 6.1 in week 1 , 17.4 + /- 6.7 in week 2 , 15.1 + /- 6.2 in week 3 , 14.0 + /- 4.8 in week 4 ) in comparison with the value of 35.3 + /- 8.7 in week -2 ) . The cough threshold for capsaicin improved from 1.70 + /- 3.04 micromol/l to 12.7 + /- 17.6 micromol/l in the epinastine group ( p < 0.05 ; baseline vs. week 4 ) The bronchial hyperresponsiveness to MCh ( Dmin ) did not change significantly either in the epinastine or the placebo groups . The morning and evening peak expiratory flow rate ( PEFR , L/min ) did not change from the baseline period in either the epinastine or the placebo groups . These results suggested that epinastine may be useful for treating patients with EB and that histamine H1-receptor is related to the pathophysiology of coughing in EB OBJECTIVES Proton-pump inhibitors are often recommended in the treatment of laryngitis secondary to gastric reflux . Despite prospect i ve treatment studies reporting high efficacy , only one previous report has been placebo-controlled and blinded . The objective of this study was to determine the efficacy of omeprazole in treating proven reflux laryngitis . STUDY DESIGN Prospect i ve , placebo-controlled , r and omized , double-blind clinical trial . METHODS Fifty-three patients with one or more reflux laryngitis symptoms were recruited to undergo 24-hour dual-channel pH probe testing .  Thirty patients with more than four episodes of laryngopharyngeal reflux were enrolled . By r and om assignment , 15 patients received 40 mg omeprazole twice a day and the other 15 received placebo for a period of 2 months . Symptoms ( hoarseness , throat pain , lump in throat sensation , throat clearing , cough , excessive phlegm , dysphagia , odynophagia , and heartburn ) and endoscopic laryngeal signs ( erythema , edema , and mucus accumulation ) were recorded initially , at 1 month , and 2 months . RESULTS In general , most symptom scores improved over time for both the omeprazole and placebo groups . Hoarseness , when patients begin with low hoarseness symptom scores , and throat clearing improved significantly more in patients on omeprazole than in those on placebo during the 2-month study . Throat pain , lump in throat sensation , excessive phlegm , difficulty swallowing , pain with swallowing , and heartburn showed improvement in both treatment arms , signifying the possibility of a placebo effect . Endoscopic laryngeal signs did not change significantly over the course of the study for either treatment group . CONCLUSIONS A placebo effect appears to exist in the treatment of reflux laryngitis . However , hoarseness , when initially scored low , and throat clearing result ing from reflux laryngitis are effectively treated by omeprazole Thirty‐one patients with a dry cough for at least 1 h duration in more than half of the last 30 days and with no recent respiratory infection participated in a clinical trial to evaluate the effect of inhaled beclomethasone dipropionate ( BDP ) . Lung function was normal and reversibility was excluded by spirometry before and after bronchodilator and by no diurnal variation in home peak flow monitoring . Only one had significant eosinophilia and only three were mildly hyperreactive by bronchial provocation with histamine . After a 1‐week run‐in period the patients were r and omly allocated to receive either BDP 4 puffs of 50 μg b.i.d . , or placebo . After 2 weeks the patients were crossed over and received the alternative treatment for another 2‐week period . The degree of cough , disturbance of night sleep and peak expiratory flow morning and evening were recorded daily in a diary . Spirometry was performed at each control visit . A significant period effect from run‐in to period 1 and /or from period 1 to period 2 was demonstrated for cough and disturbance at night but not for peak flow or spirometry . However , no significant treatment effect was found for any of the measured variables This multicentre , double-blind , placebo controlled , between-patient study in general practice in the United Kingdom examined the effect of oral N-acetylcysteine ( Fabrol ® ) on the symptomatology of patients with chronic bronchitis over a 3-month period . Although improvement in subjective symptoms ( sputum viscosity and character , difficulty in expectoration and cough severity ) occurred in both treatment groups over the trial period , improvements in difficulty in expectoration and cough severity were greater in patients receiving N-acetylcysteine compared to matching placebo . Trial medication was well tolerated , with a greater number of side-effects attributed to therapy occurring in patients receiving placebo Home peak expiratory flow ( PEF ) measurement is recommended by asthma guidelines . In a 16-week r and omized controlled study on 16 subjects with asthma ( 24.6 6.5 years old , asthma duration small ze , Cyrillic 6 months ) , we examined Global System for Mobile Communications ( GSM ) mobile telephone short-message service ( SMS ) as a novel means of telemedicine in PEF monitoring . All subjects received asthma education , self-management plan , and st and ard treatment . All measured PEF three times daily and kept a symptom diary . In the study group , therapy was adjusted weekly by an asthma specialist according to PEF values received daily from the patients . There was no significant difference between the groups in absolute PEF , but PEF variability was significantly smaller in the study group ( 16.12 + /- 6.93 % vs. 27.24 + /- 10.01 % , p = 0.049 ) . forced expiratory flow in 1 second ( FEV1 ; % predicted ) in the study group was slightly but significantly increased ( 81.25 + /- 17.31 vs. 77.63 + /- 14.80 , p = 0.014 ) and in the control group , unchanged ( 78.25 + /- 21.09 vs. 78.88 + /- 22.02 , p = 0.497 ) . Mean FEV1 was similar in the two groups both before and after the study . Controls had significantly higher scores for cough ( 1.85 + /- 0.43 vs. 1.42 + /- 0.28 , p < 0.05 ) and night symptoms ( 1.22 + /- 0.23 vs. 0.85 + /- 0.32 , p < 0.05 ) . There was no significant difference between the groups in daily consumption of inhaled medicine , forced vital capacity , or compliance . Per patient , per week , the additional cost of follow-up by SMS was Euros 1.67 ( equivalent to approximately $ 1.30 per 1 Euro ) , and SMS transmission required 11.5 minutes . Although a study group of 40 patients is needed for the follow-up study to achieve the power of 80 % within the 95 % confidence interval , we conclude that SMS is a convenient , reliable , affordable , and secure means of telemedicine that may improve asthma control when added to a written action plan and st and ard follow-up The efficacy and safety of once-daily beclomethasone dipropionate ( BDP ; 200 μg ) , in combination with the propellant hydrofluoroalkane-134a ( HFA ) was compared with that of budesonide turbuhaler ( BUD-TH ) 400 μg twice daily and fluticasone propionate inhaler ( FP-IH ) 250 μg twice daily in 40 patients with bronchial asthma or chronic obstructive pulmonary disease . All patients had used inhaled corticosteroids for at least 1 month . On r and omization , 20 patients were switched to HFA-BDP and 20 patients remained on their existing BUD-TH or FP-IH treatment . After 8 weeks , HFA – BDP demonstrated a greater improvement in spirometric values , respiratory symptoms and β2-agonist use . No significant local adverse effects were observed . Blood cortisol levels remained in the normal range in both groups . We conclude that HFA – BDP ( 200 μg once-daily ) offered more benefit in terms of clinical and spirometry indices than BUD-TH ( 400 μg twice daily ) or FP-IH ( 250 μg twice daily ) in patients with moderate asthma and chronic obstructive pulmonary disease The efficacy and safety of nedocromil sodium inhalation aerosol ( 4 mg of Tilade administered by metered-dose inhaler ) given twice daily was compared with placebo in 112 patients with mild-to-moderate asthma who had been receiving maintenance therapy with oral or inhaled bronchodilators or both . After a 2-week run-in period and a subsequent 2-week baseline period , patients were r and omized to active treatment ( n = 56 ) or placebo ( n = 56 ) for 8 weeks . All maintenance bronchodilators were withdrawn before the baseline period , and patients entered the treatment period only after demonstrating a specified level of asthma symptoms . Twice daily administration of nedocromil sodium improved all asthma symptoms in these patients who had symptoms as a result of the withdrawal of their maintenance theophylline and /or oral and inhaled beta 2-agonist bronchodilators . During the primary time period ( treatment weeks 5 to 8) , statistically significant between-group differences favored nedocromil sodium for the asthma summary score ( primary variable , p = 0.001 ) , daytime asthma ( p = 0.001 ) , and sleep difficulty caused by asthma ( p = 0.006 ) . Furthermore , significant reductions in the use of as-needed rescue medications were reported in the nedocromil sodium group ( p = 0.003 ) compared with the placebo group . Final overall opinions of treatment effectiveness expressed by physicians ( p = 0.016 ) and patients ( p = 0.002 ) strongly favored nedocromil sodium BACKGROUND The synthetic mucolytic neltene-xine is an amide derivative of ambroxol and thiophencarboxylic acid . The aim of this open , r and omised , controlled study versus sobrerol was to evaluate the efficacy and tolerability of neltenexine ( oral granules in sachets ) as compared with sobrerol ( oral granules in sachets ) , administered to patients with obstructive airways disease . METHODS Thirty male and female patients were recruited . The exclusion criteria were allergy to neltenexine or sobrerol , an assessed diagnosis of severe bronchospasm requiring beta2-agonists , corticosteroids or aminophylline , pregnant or nursing women , cystic fibrosis , active tuberculosis or an assessed diagnosis of bronchiectasis . No infections of other organs ( such as urinary tract infections ) were present at baseline . Concomitant treatment with antitussives or other mucolytic agents was not allowed during the course of the study . Fifteen patients were r and omised to treatment with neltenexine , 1 sachet thrice daily for 20 days orally ( neltenexine group ) and 15 patients to treatment with sobrerol , 1 sachet thrice daily for 20 days orally ( sobrerol group ) . The efficacy parameters were : sputum characteristics and volume , difficulty in expectorating , cough , dyspnoea , pulmonary auscultation . Tolerability was monitored and adverse events were reported . RESULTS The study highlighted that neltenexine has a good efficacy in the treatment of patients with obstructive airways disease entailing significant impairment of clinical parameters . CONCLUSIONS Neltenexine can be an effective therapeutic alternative to sobrerol Abstract Study objective . Th2 cytokines play an important role in the pathogenesis of asthma . Our study objective was to determine the effect of suplatast tosilate , a Th2 cytokine inhibitor , on patients with cough-variant asthma . Methods . Twenty patients with cough-variant asthma ( CVA ) were assigned to a suplatast tosilate ( 100 mg three times daily ) group or a placebo group for 6 weeks in a double-blind r and omized study . The cough scores , medication scores , pulmonary function , bronchial hyperresponsiveness to methacholine , cough threshold for capsaicin , percentage of eosinophils and concentrations of eosinophilic cationic protein ( ECP ) in hypertonic saline-induced ( induced ) sputum were evaluated . The main outcome measures were capsaicin cough threshold and concentrations of ECP in induced sputum . Results . In the suplatast group , the cough scores and the medication scores decreased significantly over time . The percentage of eosinophils in induced sputum significantly decreased from 53.5±5.6 % to 13.6±2.6 % . The cough threshold for capsaicin improved significantly from 2.72±3.41 µM to 39.7±22.7 µM in the suplatast group . The concentrations of ECP in induced sputum decreased significantly from 435±123 µg/l to 56±34 µg/l in the suplatast group . The bronchial responsiveness to methacholine changed from 8.45±3.43 units to 11.4±3.76 units in the suplatast group . Conclusions . Suplatast improved the cough scores and the cough threshold for capsaicin in patients with CVA without significant side effects , suggesting the effectiveness of suplatast in the treatment of CVA . Suplatast also decreased the percentage of eosinophils and concentrations of ECP in induced sputum , suggesting improvement in eosinophilic inflammation in patients with CVA . Further pharmacodynamic research is needed to explain the precise mechanism Abstract Objective : This study aim ed to compare the clinical efficacy of two anti-inflammatory medications ( fenspiride and inhaled beclomethasone [ beclomethasone dipropionate ] ) in patients with stable chronic obstructive pulmonary disease ( COPD ) over 6 months . Design , methods and patients : This was a r and omised comparison of 58 patients with COPD , divided into five treatment groups : fenspiride ( stages 1 and 2 ) , beclomethasone ( stage 2 ) , and two control groups ( stages 1 and 2 ) . In addition , 64 patients with exacerbations of COPD were evaluated over a 2-week treatment period during which they received either fenspiride or prednisolone . Clinical signs and symptoms of COPD were evaluated every 2 months ( aggregated numerical index of signs and symptoms ) , as were lung function tests ( forced vital capacity [ FVC ] , forced expiratory volume in 1 second [ FEV1 ] , FEV1/FVC ) and a 6-minute walking test . Results : Statistically significant reductions in all evaluated COPD signs and symptoms were achieved with fenspiride in stage 1 COPD . Fenspiride therapy significantly reduced the indices of sputum parameters ( 8-fold decrease ) , incidence of dry rales ( 6-fold decrease ) , dyspnoea ( 4-fold decrease ) and cough ( 2.5-fold decrease ) . In comparison with beclomethasone , fenspiride was superior in stage 2 COPD . In patients with stage 2 COPD , reductions were less marked , but remained significantly superior in the fenspiride group in comparison with the beclomethasone group and the control groups . In patients with exacerbations of COPD , fenspiride had equivalent efficacy to that of systemic corticosteroids . Conclusion : Anti-inflammatory therapy with fenspiride in addition to bronchodilators significantly improved clinical signs and symptoms , external respiratory function tests and physical activity tests in patients with stage 1 COPD . Adjunctive fenspiride therapy was superior to inhaled beclomethasone in stage 2 COPD . Anti-inflammatory therapy in COPD may be more effective at an early stage of this disease In a double-blind study we compared the effect of 2 mg ketotifen ( Zaditen ) daily and 1050 mg aminophylline daily for 6 months in two groups of altogether 24 patients with bronchial asthma and a chronic obstruction of the airways . Lung function tests were done in regular intervals to investigate the effects of the drugs on the central airways resistance , thoracic gas volume , forced expiratory volume of the first second and inspiratory vital capacity-- and the peripheral airways closing volume , flow of iso and the flow volume curve .  Ketotifen reduced the obstruction of the central and of the peripheral airways .  Aminophylline showed a less pronounced effect on the obstruction of the central airways and did not influence the peripheral airways . Number and severity of asthmatic attacks , cough , dyspnea and expectoration improved with both drugs . From our results we conclude that ketotifen reduces the obstruction of the central airways and also may exert a direct influence on the small airways . This drug therefore seems to possess special antiasthmatic effects . In contrast aminophylline acts as a rapidly effective bronchodilating agent with no detectable effects on the peripheral airways The effects of nedocromil sodium were assessed in 110 patients with asthma who experienced asthma symptoms despite the use of high doses of inhaled bronchodilators . During the baseline period , antiinflammatory agents were not permitted , and patients were treated with inhaled beta-agonists on an as-needed basis . Patients who required 12 or more puffs of albuterol and experienced continuing asthma symptoms for 7 of the 14 baseline days were r and omized to treatment groups . Subjects received either nedocromil sodium ( 4 mg ) or placebo four times a day for 10 weeks . Statistically significant ( p < 0.05 ) between-treatment differences ( weeks 3 to 10 ) , favoring nedocromil sodium , were determined for the asthma summary score , daytime asthma severity , asthmatic cough , morning peak flow rates , reduction of as-needed bronchodilator use , physician 's assessment of asthma severity , and patient and physician opinions of treatment effectiveness . By trial end ( week 10 ) , sleep difficulty caused by asthma decreased 29 % in the nedocromil sodium group and 4 % in the placebo group ( p = 0.006 ) . Nedocromil sodium was well tolerated and improved asthma control while reducing the inhaled bronchodilator load of these patients with moderately severe asthma STUDY OBJECTIVES Cough is the most common complaint for which patients in the United States seek medical attention . Although the significant effect of cough on quality of life has been reported , the association of chronic cough with depressive symptomatology has not previously been investigated . DESIGN Prospect i ve , nonr and omized evaluation . SETTING Outpatient department of academic medical center . PATIENTS Representative sample of patients presenting to a specialty center seeking evaluation and treatment of chronic cough . INTERVENTIONS Participants completed the Center for Epidemiologic Studies Depression Scale ( CES-D ) , a 20-item self-report question naire design ed to measure depressive symptomatology and risk for clinical depression , on initial evaluation and again after 3 months . Patients also provided  subjective cough scores  reflecting the severity of their cough . MEASUREMENTS AND RESULTS Of 100 patients undergoing initial evaluation , 53 % scored positive ( > /= 16 ) on the CES-D. Mean CES-D score was 18.3 + /- 13.2 ( + /- SD ) . Among 81 subjects followed up at 3 months , mean CES-D score fell to 7.4 + /- 10.4 , and subjective cough score decreased from 10 to 4.9 + /- 3.1 . There was a statistically significant improvement in both cough and depression scores after 3 months ( p < 0.001 ) . Improvement in cough score correlated significantly with improvement in depression score ( p = 0.003 ; Spearman rho = 0.323 ) . CONCLUSION Depressive symptomatology is very common in patients with chronic cough . Physicians and other caregivers must be aware of the significant risk of clinical depression in this patient population Hydrofluoroalkane-134a ( HFA-134a ) is a new chlorofluorocarbon (CFC)-free propellant for use in metered dose inhalers . It provides a more environmentally friendly alternative to CFC propellants because it does not contain chlorine which is responsible for ozone depletion by CFCs . Beclomethasone dipropionate ( BDP ) is widely used for inhalation asthma therapy and is most commonly delivered by a CFC propellant system . The present study evaluated the acute safety of BDP formulated with the new propellant ( HFA-134a BDP ) compared with BDP in a CFC-11/12 formulation by measuring the acute bronchial response in asthmatic patients . The study was conducted as a r and omized , single-blind , placebo-controlled , four-period cross-over trial . Asthmatic patients received eight inhalations of four treatment regimens ( HFA-134a BDP , 1600 mg total dose ; CFC-11/12 BDP , 2000 mg total dose ; HFA-134a placebo and CFC-11/12 placebo ) in r and om order over four study days . Forced expired volume in 1 s ( FEV1 ) was measured before and 2 , 10 , 20 , 40 and 60 min after inhalation of the study treatments . The number of coughs was counted from the start of the first inhalation to 60 s after the last inhalation . There were no statistically significant differences between the treatment groups for changes in FEV1 , for the number of coughs or for the occurrence or severity of bronchoconstriction . In asthmatic patients withholding bronchodilators , the new HFA-134a BDP propellant system proved as safe and was as well tolerated as the current CFC-11/12 BDP system . The two propellant systems without active drug were also equally well tolerated In a double-blind trial , 29 patients were treated for stable , chronic bronchitis with iodinated glycerol ( Organidin , 60 mg four times daily ; n = 16 ) or placebo ( n = 13 ) . The study consisted of a 2-week single-blind lead-in period , followed by a 6-week double-blind treatment period , and assessed a total of 50 response variables . In this set of patients , treatment with iodinated glycerol was associated with statistically significant ( P < 0.05 ) and /or positive trend ( P < 0.1 ) toward improvement in cough frequency , cough severity , difficulty in raising sputum , sputum thickness , sputum stickiness , forced expiratory flow at FVC25%-75 % , cell concentration in sputum , and several measures of physician assessment of patient condition .  Iodinated glycerol was well tolerated during the 6-week treatment period ; no adverse effects were reported and no patient receiving iodinated glycerol withdrew from the study prematurely . In conclusion , this study demonstrates that iodinated glycerol , 60-mg tablets given in a total daily dose of 240 mg , is safe and effective therapy for reducing symptoms in patients with stable , chronic bronchitis
The management of cough in adults with respiratory and non-respiratory illnesses is suboptimal and based mostly on clinical opinions rather than evidence .