In-hospital antibiotic use for severe chronic obstructive pulmonary disease exacerbations: a retrospective observational study.

BACKGROUND: The use of antibiotics in mild to severe acute exacerbations of chronic obstructive pulmonary disease (COPD) remains controversial. AIM: To explore in-hospital antibiotic use in severe acute exacerbations of COPD (AECOPD), to analyze determinants of in-hospital antibiotic use, and to investigate its association with hospital length of stay (LOS) and in-hospital mortality. METHODS: A retrospective, observational study was conducted in Ghent University Hospital. Severe AECOPD were defined as hospitalizations for AECOPD (ICD-10 J44.0 and J44.1) discharged between 2016 and 2021. Patients with a concomitant diagnosis of pneumonia or 'pure' asthma were excluded. An alluvial plot was used to describe antibiotic treatment patterns. Logistic regression analyses identified determinants of in-hospital antibiotic use. Cox proportional hazards regression analyses were used to compare time to discharge alive and time to in-hospital death between antibiotic-treated and non-antibiotic-treated AECOPD patients. RESULTS: In total, 431 AECOPD patients (mean age 70 years, 63% males) were included. More than two-thirds (68%) of patients were treated with antibiotics, mainly amoxicillin-clavulanic acid. In multivariable analysis, several patient-related variables (age, body mass index (BMI), cancer), treatment-related variables (maintenance azithromycin, theophylline), clinical variables (sputum volume and body temperature) and laboratory results (C-reactive protein (CRP) levels) were associated with in-hospital antibiotic use independent of sputum purulence, neutrophil counts, inhaled corticosteroids and intensive care unit of which CRP level was the strongest determinant. The median hospital LOS was significantly longer in antibiotic-treated patients (6 days [4-10]) compared to non-antibiotic-treated patients (4 days [2-7]) (p < 0.001, Log rank test). This was indicated by a reduced probability of hospital discharge even after adjustment for age, sputum purulence, BMI, in-hospital systemic corticosteroid use and forced expiratory volume in one second (FEV1) (adjusted hazard ratio 0.60; 95% CI 0.43; 0.84). In-hospital antibiotic use was not significantly associated with in-hospital mortality. CONCLUSIONS: In this observational study in a Belgian tertiary hospital, in-hospital antibiotic use among patients with severe AECOPD was determined by the symptom severity of the exacerbation and the underlying COPD severity as recommended by the guidelines, but also by patient-related variables. Moreover, in-hospital antibiotic use was associated with a longer hospital stay, which may be linked to their disease severity, slower response to treatment or 'harm' due to antibiotics. TRIAL REGISTRATION: Number: B670201939030; date of registration: March 5, 2019.

Serum Immunoglobulins, Pneumonia Risk, and Lung Function in Middle-Aged and Older Individuals: A Population-Based Cohort Study.

Introduction: Immunoglobulins (Igs) play a pivotal role in host defense and prevention of pneumonia. Aging influences serum Ig levels, but the association between Igs and pneumonia in community-dwelling older individuals remains unknown. We evaluated the association of serum IgA, IgG, and IgM with pneumonia and lung function in middle-aged and older individuals. Methods: We performed Cox and negative binomial regression analyses for the association of Igs with incident pneumonia and pneumonia-related mortality, and recurrent pneumonia respectively. We performed logistic regression analyses for the association between Igs and lung function values. Associations were adjusted for age, sex, smoking, comorbidities, and serum C-reactive protein. Results: We included 8,766 participants (median age 62.2 years, 57% women, median follow-up 9.8 years). Higher IgA (hazard ratio [HR]: 1.15; 95% confidence interval [95% CI]: 1.00-1.32) and IgG (HR: 1.13; 95% CI: 1.06-1.19) were associated with an increased pneumonia risk. Higher IgG was associated with an increased risk of pneumonia-related mortality (HR: 1.08; 95% CI: 1.01-1.16) and recurrent pneumonia (incidence rate ratio: 1.04; 95% CI: 1.00-1.09). Higher IgA and IgG were also associated with lower forced expiratory volume in one second (FEV1), lower forced vital capacity (FVC), and an increased odds of preserved ratio impaired spirometry (PRISm, i.e. FEV1 <80% and FEV1/FVC ratio ≥70%). No association was seen with an obstructive spirometry pattern. Discussion: Higher serum IgA and IgG levels were associated with pneumonia, pneumonia-related mortality, and PRISm in middle-aged and older individuals from the general population. Future studies should validate our findings and elucidate underlying pathophysiology.

Determinants of poor inhaler technique and poor therapy adherence in obstructive lung diseases: a cross-sectional study in community pharmacies.

BACKGROUND: Correct inhaler use can be challenging in real life, with incorrect use resulting in poor symptom control. The aim of this study was to examine factors associated with poor inhaler technique and poor therapy adherence among patients with obstructive lung disease in community pharmacies. METHODS: A cross-sectional study was conducted in patients with obstructive lung diseases in nine Belgian community pharmacies. Logistic regression analyses identified factors associated with poor inhaler technique and poor therapy adherence (assessed by the Test of Adherence to Inhalers and the modified Medication Possession Ratio). RESULTS: Seventy obstructively impaired community patients (median age 64 y, 56% females) were included and the technique of 122 inhalers was assessed. Inhaler technique scored generally poor, with half of patients making critical errors in using at least one of their inhalers. In multivariable analysis, the use of multiple devices (adjusted OR, aOR 11.68; 95% CI 3.29 to 41.51) and a diagnosis of asthma-Chronic Obstructive Pulmonary Disease overlap (ACO; aOR 7.06; 95% CI 1.15 to 43.35), were associated with making critical errors in inhaler technique independent of quality of life. Non-adherence occurred in more than one-third of patients, and occurred in up to one half of the patients when also taking overuse into account. In multivariable analysis for therapy adherence, current smoking was associated with poor therapy adherence (aOR 0.15; 95% CI 0.02 to 0.96) independently of age and poor treatment knowledge. Therapy adherence was poor in patients with asthma compared with those with ACO. Current smokers and highly educated patients seemed to be at increased risk for inhaler overuse. CONCLUSIONS: Given the important role of a correct inhaler technique and therapy adherence in disease control, these findings emphasise the need for patient education and aiming uniformity in the inhaler device. TRIAL REGISTRATION NUMBER: B670201835229.

Macrolide-associated ototoxicity: a cross-sectional and longitudinal study to assess the association of macrolide use with tinnitus and hearing loss.

BACKGROUND: Macrolides are widely prescribed antibiotics for many different indications. However, there are concerns about adverse effects such as ototoxicity. OBJECTIVES: To investigate whether macrolide use is associated with tinnitus and hearing loss in the general population. METHODS: Cross-sectional (n = 4286) and longitudinal (n = 636) analyses were performed within the population-based Rotterdam Study. We investigated with multivariable logistic regression models the association between macrolides and tinnitus, and with multivariable linear regression models the association between macrolides and two different hearing thresholds (both ears, averaged over 0.25, 0.5, 1, 2, 4 and 8 kHz and 2, 4 and 8 kHz). Both regression models were adjusted for age, sex, systolic blood pressure, alcohol, smoking, BMI, diabetes, education level, estimated glomerular filtration rate and other ototoxic or tinnitus-generating drugs. Cumulative exposure to macrolides was categorized according to the number of dispensed DDDs and duration of action. RESULTS: In the fully adjusted model, ever use of macrolides was associated with a 25% higher likelihood of prevalent tinnitus (OR = 1.25; 95% CI 1.07-1.46). This association was more prominent in participants with a cumulative dose of more than 14 DDDs and among users of intermediate- or long-acting macrolides. Macrolide use in between both assessments was associated with more than a 2-fold increased risk on incident tinnitus. No general association between macrolides and hearing loss was observed. A borderline significant higher hearing threshold in very recent users (≤3 weeks) was found. CONCLUSIONS: Macrolide use was significantly associated with both prevalent and incident tinnitus. Macrolide-associated tinnitus was likely cumulative dose-dependent.