Evaluation of antitussive agents in man. Salbutamol vs. placebo for treatment of pertussis. Application and validation of a computerized cough acquisition system for objective monitoring of acute cough: a meta-analysis. Optimizing antibiotic prescribing for acute cough in general practice: a cluster-randomized controlled trial. Whooping cough treated with pertussis immune serum, human; report on a controlled series of 52 patients under 1 year of age. Children with persistent cough--outcome with treatment and role of Moraxella catarrhalis? Clinical efficacy of anti-pneumococcal vaccination in patients with COPD.
Methodology to evaluate the efficacy of antitussive drugs rely largely on subjective methods and cough counts. There are few studies in cough due to natural disease especially using objective techniques. This paper presents data from a series of randomized, double blind, placebo controlled clinical trials in cough due to both chronic bronchopulmonary disease and acute upper respiratory tract infections. In these studies, cough was quantified using a standardized and validated computerized system for the acquisition and multidimensional analysis of the cough sound. Key objective parameters like cough counts, intensity, latency and total effort expended were studied. Guaiphenesin and bromhexine showed significant expectorant effects in patients with productive cough due to chronic bronchopulmonary disease. Differences were observed in speed of action, and objective and subjective measures, that probably indicate differences in drug action. More recently, three studies evaluated the antitussive drug dextromethorphan in non-productive cough due to uncomplicated upper respiratory tract infections. Reproducible cough suppressant effects were demonstrated after a single 30 mg dose using objective measures of cough counts, latency and total effort. These results establish the sensitivity and robustness of the cough quantitation methodology in the objective evaluation of cough treatments. The efficacy of salbutamol was assessed in a double blind placebo controlled crossover study in nine hospitalized children with whooping cough in the convulsive stage verified by culture or serology. The children were 1.5 to 27 months old (median, 4 months). The dosage of salbutamol was the one normally used and supplementary treatment was standardized. Salbutamol was found to give no significant effects on the course or severity of whooping cough in the children treated. The purpose of the meta-analysis was to understand the antitussive effect of treatment with dextromethorphan hydrobromide, 30 mg, vs placebo over a 3-h treatment period in patients with cough due to uncomplicated upper respiratory tract infection (URTI), and to show that the computerized system for acquisition and analysis of cough sound was consistent and reproducible across the individual studies.
                The six studies used for the meta-analysis were randomized, double-blind, parallel-group, single-dose, placebo-controlled studies with a 3-h postdose cough evaluation period.
                One study was conducted in Durban, South Africa, and five studies were conducted in Bombay, India. Four studies took place in clinics, and two studies were in-home studies.
                Seven hundred ten adult patients with cough due to uncomplicated URTI who were otherwise healthy and who satisfied the inclusion/exclusion criteria for the meta-analysis. Measurements and results: For each patient, a standard baseline was calculated pretreatment, then a 3-h continuous cough recording was made after treatment was initiated. Five efficacy variables were measured in 30-min intervals: cough bouts, cough components, cough effort, cough intensity, and cough latency. The meta-analysis showed consistent results across most of the studies for each of the efficacy variables. It demonstrated significantly greater overall reductions in cough bouts, cough components, and cough effort, and an increase in cough latency for patients treated with dextromethorphan hydrobromide, 30 mg, vs those treated with placebo.
                The results of a meta-analysis of the six clinical studies show that the antitussive effect of a single dose of dextromethorphan hydrobromide, 30 mg, has been established. The consistent nature of the results shows that the computerized cough acquisition and analysis system is a valid and reproducible methodology for evaluating cough associated with URTI. To assess the effect of a tailored professional intervention, including academic detailing, on antibiotic prescribing for acute cough.
                In a cluster-randomized controlled before and after study 85 Flemish GPs included adult patients with acute cough consulting in the periods February-April 2000 and 2001. The intervention consisted of a clinical practice guideline for acute cough, an educational outreach visit and a postal reminder to support its implementation in January 2001. Antibiotic prescribing rates and patients' symptom resolution were the main outcome measures.
                Thirty-six of 42 GPs received the intervention and 35 of 43 GPs served as controls; 1503 patients were eligible for analysis. Only in the intervention group were patients less likely to receive antibiotics after the intervention [OR(adj) (95% CI)=0.56 (0.36-0.87)]. Prescribed antibiotics were also more in line with the guideline in the intervention group [1.90 (0.96-3.75)] and less expensive from the perspective of the National Sickness and Invalidity Insurance Institute [MD(adj) (95% CI)= Euro -6.89 [-11.77-(-2.02)]]. No significant differences were found between the groups for the time to symptom resolution.
                An (inter)actively delivered tailored intervention implementing a guideline for acute cough is successful in optimizing antibiotic prescribing without affecting patients' symptom resolution. Further research efforts should be devoted to cost-effectiveness studies of such interventions. nan 52 children with severe cough persisting for more than 10 days were randomized to treatment with amoxycillin/clavulanic acid or placebo in a prospective double-blinded study. Clinically suspected cases of pertussis were excluded, yet 12 (23%) of the children had laboratory verified pertussis infection. The nasopharyngeal colonization showed a predominance of Moraxella catarrhalis which was isolated in 37 (71%) children. Streptococcus pneumoniae and Haemophilus influenzae were isolated in 11 (20%) and 16 (30%) children, respectively. The antibiotic-treated group had a significantly better recovery in both the pediatrician's estimation (p = 0.02) and the independent parental judgement (p = 0.002). These findings are consistent with the view that Moraxella catarrhalis could be directly involved in the pathogenesis of persistent cough in children. A study was undertaken to evaluate the clinical efficacy of the 23-valent pneumococcal polysaccharide vaccine (PPV) in immunocompetent patients with chronic obstructive pulmonary disease (COPD).
                A randomised controlled trial was carried out in 596 patients with COPD of mean (SD) age 65.8 (9.7) years, 298 of whom received PPV. The main outcome was radiographically proven community acquired pneumonia (CAP) of pneumococcal or unknown aetiology after a mean period of 979 days (range 20-1454).
                There were 58 first episodes of CAP caused by pneumococcus or of unknown aetiology, 25 in the intervention group and 33 in the non-intervention group. Kaplan-Meier survival curves for CAP did not show significant differences between the intervention and non-intervention arms (log rank test = 1.15, p = 0.28) in the whole group of patients. The efficacy of PPV in all patients was 24% (95% CI -24 to 54; p = 0.333). In the subgroup aged <65 years the efficacy of PPV was 76% (95% CI 20 to 93; p = 0.013), while in those with severe functional obstruction (forced expiratory volume in 1 second <40%) it was 48% (95% CI -7 to 80; p = 0.076). In younger patients with severe airflow obstruction the efficacy was 91% (95% CI 35 to 99; p = 0.002). There were only five cases of non-bacteraemic pneumococcal CAP, all in the non-intervention group (log rank test = 5.03; p = 0.025). Multivariate analysis gave a hazard ratio for unknown and pneumococcal CAP in the vaccinated group, adjusted for age, of 0.20 (95% CI 0.06 to 0.68; p = 0.01).
                PPV is effective in preventing CAP in patients with COPD aged less than 65 years and in those with severe airflow obstruction. No differences were found among the other groups of patients with COPD.
There is insufficient evidence to draw conclusions about the effectiveness of interventions for the cough in whooping cough.