Systemic antibiotics for Pseudomonas aeruginosa infection in outpatients with non-hospitalised exacerbations of pre-existing lung diseases: a randomised clinical trial.

BACKGROUND: The effect of dual systemic antibiotic therapy against Pseudomonas aeruginosa in patients with pre-existing lung disease is unknown. To assess whether dual systemic antibiotics against P. aeruginosa in outpatients with COPD, non-cystic fibrosis (non-CF) bronchiectasis, or asthma can improve outcomes. METHODS: Multicenter, randomised, open-label trial conducted at seven respiratory outpatient clinics in Denmark. Outpatients with COPD, non-CF bronchiectasis, or asthma with a current P. aeruginosa-positive lower respiratory tract culture (clinical routine samples obtained based on symptoms of exacerbation not requiring hospitalisation), regardless of prior P. aeruginosa-status, no current need for hospitalisation, and at least two moderate or one hospitalisation-requiring exacerbation within the last year were eligible. Patients were assigned 1:1 to 14 days of dual systemic anti-pseudomonal antibiotics or no antibiotic treatment. Primary outcome was time to prednisolone or antibiotic-requiring exacerbation or death from day 20 to day 365. RESULTS: The trial was stopped prematurely based in lack of recruitment during the COVID-19 pandemic, this decision was endorsed by the Data and Safety Monitoring Board. Forty-nine outpatients were included in the study. There was a reduction in risk of the primary outcome in the antibiotic group compared to the control group (HR 0.51 (95%CI 0.27-0.96), p = 0.037). The incidence of admissions with exacerbation within one year was 1.1 (95%CI 0.6-1.7) in the dual antibiotic group vs. 2.9 (95%CI 1.3-4.5) in the control group, p = 0.037. CONCLUSIONS: Use of dual systemic antibiotics for 14 days against P. aeruginosa in outpatients with chronic lung diseases and no judged need for hospitalisation, improved clinical outcomes markedly. The main limitation was the premature closure of the trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03262142, registration date 2017-08-25.

Targeted AntiBiotics for Chronic pulmonary diseases (TARGET ABC): can targeted antibiotic therapy improve the prognosis of Pseudomonas aeruginosa-infected patients with chronic pulmonary obstructive disease, non-cystic fibrosis bronchiectasis, and asthma? A multicenter, randomized, controlled, open-label trial.

BACKGROUND: Pseudomonas aeruginosa infection is seen in chronic pulmonary disease and is associated with exacerbations and poor long-term prognosis. However, evidence-based guidelines for the management and treatment of P. aeruginosa infection in chronic, non-cystic fibrosis (CF) pulmonary disease are lacking. The aim of this study is to investigate whether targeted antibiotic treatment against P. aeruginosa can reduce exacerbations and mortality in patients with chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis, and asthma. METHODS: This study is an ongoing multicenter, randomized, controlled, open-label trial. A total of 150 patients with COPD, non-CF bronchiectasis or asthma, and P. aeruginosa-positive lower respiratory tract samples will be randomly assigned with a 1:1 ratio to either no antibiotic treatment or anti-pseudomonal antibiotic treatment with intravenous beta-lactam and oral ciprofloxacin for 14 days. The primary outcome, analyzed with two co-primary endpoints, is (i) time to prednisolone and/or antibiotic requiring exacerbation or death, in the primary or secondary health sector, within days 20-365 from study allocation and (ii) days alive and without exacerbation within days 20-365 from the study allocation. DISCUSSION: This trial will determine whether targeted antibiotics can benefit future patients with chronic, non-CF pulmonary disease and P. aeruginosa infection in terms of reduced morbidity and mortality, thus optimizing therapeutic approaches in this large group of chronic patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03262142 . Registered on August 25, 2017.

TOB-STOP-COP (TOBacco STOP in COPd trial): study protocol-a randomized open-label, superiority, multicenter, two-arm intervention study of the effect of "high-intensity" vs. "low-intensity" smoking cessation intervention in active smokers with chronic obstructive pulmonary disease.

BACKGROUND: Cigarette smoking is the leading cause of chronic obstructive pulmonary disease (COPD), and it contributes to the development of many other serious diseases. Smoking cessation in COPD patients is known to improve survival and reduce the number of hospitalization-requiring acute exacerbations of COPD. However, smoking cessation interventions in these patients have only been successful for approximately 15-20% for consistent smoking abstinence in 12 months. Thus, more effective interventions are needed for this patient group. The aim of this study is to determine whether a high-intensity intervention compared to a low-intensity intervention can increase the proportion of persistent (> 12 months) anamnestic and biochemical smoking cessation in active smokers with COPD. METHODS: This study is a randomized controlled trial. A total of 600 active smokers with COPD will be randomly assigned 1:1 to either a standard treatment (guideline-based municipal smoking cessation program, "low intensity" group) or an intervention ("high-intensity" group) group, which consists of group sessions, telephone consultations, behavior design, hotline, and "buddy-matching" (smoker matched with COPD patient who has ceased smoking). Both groups will receive pharmacological smoking cessation. The primary endpoint is anamnestic and biochemical (cotinine analysis in urine) validated smoking cessation after 12 months. DISCUSSION: The potential benefit of this project is to improve smoking cessation rates and thereby reduce smoking-related exacerbations of COPD. In addition, the project can potentially benefit from increasing the quality of life and longevity of COPD patients and reducing the risk of other smoking-related diseases. TRIAL REGISTRATION: ClinicalTrials.gov NCT04088942 . Registered on 13 September 2019.

Passive smoking is associated with poor asthma control during pregnancy: a prospective study of 500 pregnancies.

BACKGROUND AND AIM: Asthma and tobacco exposure is common among pregnant women. We investigated the effect of passive and active smoking on asthma control during pregnancy. METHODS: Prospective observational design. Patients had their asthma control, based on symptoms, use of medication, spirometry, and exhaled nitric oxide [FENO], assessed every four weeks during 2nd and 3rd trimester of pregnancy; data on tobacco exposure were also collected prospectively. The primary outcome was episodes of uncontrolled and partly controlled asthma during pregnancy (defined according to GINA-guidelines). RESULTS: A total of 500 pregnant women with asthma (mean age 30.8 years, range 17 to 44) were consecutively included, of whom 32 (6.4%), 115 (23.0%) and 353 (70.6%), respectively, were current smokers, ex-smokers and never smokers [NS]. Sixty-five NS (18.4%) reported passive tobacco exposure. NS with passive tobacco exposure had significantly lower FEV1% predicted (p<0.02) and FENO (p = 0.01) compared to NS without passive tobacco exposure. The relative risk [RR] of an episode of uncontrolled asthma during pregnancy was 4.5 (95% CI 2.7-7.5: p<0.001) in current and ex-smokers compared with never smokers, and 2.9 (95% CI 1.4-5.9; p = 0.004) in NS-women with passive tobacco exposure compared with NS-women not reporting passive tobacco exposure. Treatment with inhaled corticosteroids, most likely as a marker of more severe asthma, was also associated with a higher risk (RR 8.1, 95% CI 5.1-13.0; p<0.001) of an episode of uncontrolled asthma. CONCLUSION: Passive tobacco exposure in never smokers is associated with an increased risk of episodes of uncontrolled asthma during pregnancy, which is likely to have adverse effects on pregnancy outcome.

[Hypercalcaemia can be the only initial symptom of sarcoidosis].

Sarcoidosis is an ordinary systemic inflammatory disease that can affect many organs. It is characterized by development of non-necrotizing granulomas. It commonly affects lungs (80%) while hypercalcaemia is found in 5% and reflects an activation of T-cells within the granulomas that causes an overproduction of 1,25-dihydroxyvitamin D3. We describe a case where hypercalcaemia was the only symptom in a patient with extrapulmonary sarcoidosis, and the investigation was misled by different serologic findings though PET-CT showed fludeoxyglucose uptake in the biceps femoris muscles. The diagnosis was made after a biopsy.

High aortic augmentation index predicts mortality and cardiovascular events in men from a general population, but not in women.

BACKGROUND: A recent meta-analysis concluded that augmentation index (AIx), a measure of pulse wave reflections influencing the central blood pressure, is related to mortality and cardiovascular disease (CVD) events and is likely to be clinically useful. However, prospective data based on non high-risk populations and women are lacking. METHODS AND RESULTS: In a random sample comprising 1300 men and 1773 women from Copenhagen, Denmark, AIx was measured non-invasively by use of the SphygmoCor device. The population was followed prospectively for a mean of 6.5 years for all-cause mortality and a combined CVD end point (time to first myocardial infarction, ischaemic cerebrovascular disease, percutaneous coronary intervention, coronary by-pass graft, or death from any cause). In men, hazard ratio (HR) in highest AIx tertile vs. lowest was 1.68 (95% CI 1.02-2.76) for all-cause mortality and 1.60 (95% CI 1.07-2.39) for the combined CVD end point after multivariable adjustment for CVD risk factors. In women, however, AIx was not related to either outcome with adjusted HR of 0.70 (95% CI 0.46-1.05) for all-cause mortality and 1.12 (95% CI 0.78-1.58) for the combined CVD end point. CONCLUSIONS: Our findings support that AIx relates to CVD in men but question the value in women. This gender differences may relate to different development in AIx with increasing age in men and women. Further studies are needed before AIx can be considered in CVD risk stratification or clinical practice.

Aortic augmentation index: reference values in a large unselected population by means of the SphygmoCor device.

BACKGROUND: Arterial stiffness and pulse wave reflection are associated with cardiovascular disease (CVD). Pulse wave analyses (PWAs) allow the estimation of the central augmentation index (AIx), a measurement of pulse wave reflection. To understand the predictive role of AIx, reference values for AIx are needed. METHODS: This population study is based on 4,561 subjects from The Copenhagen City Heart Study, an ongoing epidemiological survey started in 1976, including subjects randomly chosen from the population in Copenhagen, Denmark. We calculated and internally validated reference values of AIx measured by the SphygmoCor device in a cohort without known CVD or diabetes, and with low risk of CVD according to HeartScore using gender-specific multiple regression analyses adjusting for age, heart rate, and height. RESULTS: AIx was significantly higher in women than in men, 30% vs. 22%, (P < 0.001) and the increase in AIx with age was curvilinear. There were 972 subjects in the low-risk cohort with mean AIx 28% in women (N = 565) and 18% in men (N = 407) (P < 0.001). We report the following internally validated reference equations for AIx: men: AIx = 79.20 + 0.63 (age) - 0.002 (age(2)) - 0.28 (heart rate) - 0.39 (height). Women: AIx = 56.28 + 0.90 (age) - 0.005 (age(2)) - 0.34 (heart rate) - 0.24 (height). AIx appeared to increase with increasing risk of CVD according to HeartScore. CONCLUSIONS: We report a novel and internally validated gender-specific equation including age, heart rate, and height to calculate reference values for AIx.