Prof. Dr. med. Andreas Zeller

Cough is one of the most common causes for seeking medical advice in general practices. Post-infectious cough is defined as lasting 3 to 8 weeks after an upper respiratory tract infection (URTI). It can be very bothersome, disabling in daily activities with substantial impact on physical and psychosocial health, leading to impaired quality of life (QoL). Recommendations for the management of post-infectious cough in primary care are scarce and incoherent. To provide a wide overview of treatment options for patients with post-infectious cough, we conducted and recently published a systematic review and meta-analysis of randomised clinical trials (RCTs) assessing the patient-relevant benefits and potential harms of available treatments. Only six eligible RCTs assessing different treatment regimens (i.e. inhaled fluticasone propionate, inhaled budesonide, salbutamol plus ipratropium-bromide, montelukast, nociception-opioid-1-receptor agonist, codeine, and gelatine) were identified. None of these RCTs found clear patient-relevant benefits and most had an unclear or high risk of bias.Post-infectious cough is thought to be mediated by inflammatory processes that are also present in exacerbations of asthma or chronic obstructive pulmonary diseases (COPD). There is strong evidence that oral corticosteroids for 5 days provide patient-relevant benefit without relevant harm for these conditions. Our systematic search identified no RCTs evaluating oral corticosteroids for post-infectious cough. Thus, a high quality RCT assessing the benefits and harms of orally administered corticosteroids for post-infectious cough is needed.Aim: To assess whether a 5-day treatment with oral corticosteroids provides patient-relevant benefits by improving the cough-related QoL and reducing the duration and intensity of post-infectious cough in adult primary care patients.Methods: The proposed study is a multicentre, 1:1 randomised, parallel-group, placebo-controlled, superiority trial with blinded patients, general practitioners (GP), and outcome assessors in a primary health care setting. We plan to include 204 patients aged 18 or older seeing their GP for a cough lasting 3 to 8 weeks following an URTI. Any concurrent disease possibly explaining the symptoms, such as pneumonia, asthma, COPD, gastroesophageal reflux disease, allergic rhinitis, or cancer will be ruled out before trial inclusion. Patients will receive oral corticosteroid treatment (equivalent of 40 mg prednisone once daily) for 5 days or placebo for 5 days.The primary outcome is cough-related QoL assessed by the Leicester Cough Questionnaire (LCQ) score 14 days after randomisation. Secondary outcomes are i) cough-related QoL (at day 7, 28, and 3 months), ii) cough-related QoL sub-domains physical, psychological, and social, iii) overall cessation of cough, iv) re-consultations at GP and/or hospitalisations, v) total adverse events (AE), and vi) serious adverse events (SAE). All outcomes will be assessed through follow-up phone calls by study nurses 7, 14, 28 days, and 3 months after randomisation. Clinical follow-up visits with the GP are at the discretion of the patient and the GP.Assumptions for sample size estimation are informed by our systematic review. 204 patients are required to detect a statistically significant minimal clinically important difference of 1.3 of the LCQ score at 14 days (primary outcome; power 80%, two-sided significance level 5%, drop-out-rate 10%). Primary analysis will be done with ANCOVA (analysis of covariance) according to the intention to treat principle. Baseline LCQ scores, duration of cough, age, sex, and smoking status will be covariates.Importance: This will be the first RCT investigating whether oral corticosteroids are beneficial and safe in patients with post-infectious cough, which would have a substantial impact on the well-being and management of these patients in Switzerland and beyond.

Reduction of corticosteroid use in outpatient treatment of exacerbated COPD – a randomized, double-blind, placebo-controlled, non-inferiority study in an outpatient setting, performed in Northwestern and Central Switzerland and Austria

Background: Chronic obstructive pulmonary disease (COPD) is a major public health issue affecting approximately five to seven percent of the Swiss population. According to current guidelines for the inpatient setting, systemic corticosteroids are most important in the treatment of acute COPD exacerbations and should be given for five to seven days. Several studies suggest that corticosteroids accelerate the recovery of the FEV1 (forced expiratory volume in one second), enhance oxygenation, decrease duration of hospitalization and improve clinical outcome. However, the additional therapeutic benefit on FEV1 recovery appears to be most distinctive in the first three to five days. No data are available on the minimal necessary corticosteroid dose and treatment duration in primary care patients with acutely exacerbated COPD. Given the fact that many patients are treated in an outpatient setting, there is an urgent need to improve evidence about COPD management in this setting. Methods: The proposed study is a prospective, double-blind, randomized controlled trial that is conducted in a primary care setting including an anticipated 470 patients with acutely exacerbated COPD. Participants receive systemic corticosteroid treatment equivalent of 40 mg prednisone daily for either five days (conventional arm, n = 235), or for three days, followed by two days of placebo (experimental arm, n = 235). Antibiotic treatment for seven days is given to all patients with CRP ≥ 50 mg/l, known diagnosis of bronchiectasis, or presenting with Anthonisen Type-I exacerbation. Additional treatment after inclusion are left at the discretion of the treating general pracititioner. Follow-up visits are performed on days three and seven by the treating general practitioners, followed by telephone interviews on das 30, 90 and 180 after inclusion into the study. Primary endpoint is the time to next exacerbation during index exacerbation, or during a six-months follow-up period, whichever occurs first. Discussion: This study is designed to assess whether a three-day course of corticosteroid treatment is not inferior to the current conventional five-day treatment course in outpatients with exacerbated COPD. Depending on the results, this trial might lead to a further reduction of cumulative corticosteroid dose in COPD patients.