Real-World Effects of Antibiotic Treatment on Acute COPD Exacerbations in Outpatients: A Cohort Study under the PharmLines Initiative

<b><i>Background:</i></b> Although antibiotic treatment is recommended for acute exacerbations of chronic obstructive pulmonary disease (AECOPD), its value in real-world settings is still controversial. <b><i>Objectives:</i></b> This study aimed to evaluate the short- and long-term effects of antibiotic treatment on AECOPD outpatients. <b><i>Methods:</i></b> A cohort study was conducted under the PharmLines Initiative. We included participants with a first recorded diagnosis of COPD who received systemic glucocorticoid treatment for an AECOPD episode. The exposed and reference groups were defined based on any antibiotic prescription during the AECOPD treatment. The short-term outcome was AECOPD treatment failure within 14–30 days after the index date. The long-term outcome was time to the next exacerbation. Adjustment for confounding was made using propensity scores. <b><i>Results:</i></b> Of the 1,105 AECOPD patients, antibiotics were prescribed to 518 patients (46.9%) while 587 patients (53.1%) received no antibiotics. The overall antibiotic use was associated with a relative risk reduction of AECOPD treatment failure by 37% compared with the reference group (adjusted odds ratio [aOR] 0.63 [95% CI: 0.40–0.99]). Protective effects were similar for doxycycline, macrolides, and co-amoxiclav, although only the effect of doxycycline was statistically significant (aOR 0.53 [95% CI: 0.28–0.99]). No protective effect was seen for amoxicillin (aOR 1.49 [95% CI: 0.78–2.84]). The risk of and time to the next exacerbation was similar for both groups. <b><i>Conclusion:</i></b> Overall, antibiotic treatment, notably with doxycycline, supplementing systemic glucocorticoids reduces short-term AECOPD treatment failure in real-world outpatient settings. No long-term beneficial effects of antibiotic treatment on AECOPD were found for the prevention of subsequent exacerbations.

Prediction of Acute COPD Exacerbation in the Swiss Multicenter COPD Cohort Study (TOPDOCS) by Clinical Parameters, Medication Use, and Immunological Biomarkers

<b><i>Background and Objective:</i></b> Whether immunological biomarkers combined with clinical characteristics measured during an exacerbation-free period are predictive of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) frequency and severity is unknown. <b><i>Method:</i></b> We measured immunological biomarkers and clinical characteristics in 271 stable chronic obstructive pulmonary disease (COPD) patients (67% male, mean age 63 years) from “The Obstructive Pulmonary Disease Outcomes Cohort of Switzerland” cohort on a single occasion. One-year follow-up data were available for 178 patients. Variables independently associated with AECOPD frequency and severity were identified by multivariable regression analyses. Receiver operating characteristic analysis was used to obtain optimal cutoff levels and measure the area under the curve (AUC) in order to assess if baseline data can be used to predict future AECOPD. <b><i>Results:</i></b> Higher number of COPD medications (adjusted incident rate ratio [aIRR] 1.17) and platelet count (aIRR 1.03), and lower FEV₁% predicted (aIRR 0.84) and IgG2 (aIRR 0.84) were independently associated with AECOPD frequency in the year before baseline. Optimal cutoff levels for experiencing frequent (&#x3e;1) AECOPD were ≥3 COPD medications (AUC = 0.72), FEV₁ ≤40% predicted (AUC = 0.72), and IgG2 ≤2.6 g/L (AUC = 0.64). The performance of a model using clinical and biomarker parameters to predict future, frequent AECOPD events in the same patients was fair (AUC = 0.78) but not superior to a model using only clinical parameters (AUC = 0.79). The IFN-lambda rs8099917GG-genotype was more prevalent in patients who had severe AECOPD. <b><i>Conclusions:</i></b> Clinical and biomarker parameters assessed at a single point in time correlated with the frequency of AECOPD events during the year before and the year after assessment. However, only clinical parameters had fair discriminatory power in identifying patients likely to experience frequent AECOPD.

Implementation of Bronchoscopic Lung Volume Reduction Using One-Way Endobronchial Valves: A Retrospective Single-Centre Cohort Study

<b><i>Background:</i></b> Bronchoscopic lung volume reduction (BLVR) using 1-way endobronchial valves (EBV) has become a guideline treatment in patients with advanced emphysema. Evidence from this minimally invasive treatment derives mainly from well-designed controlled trials conducted in high-volume specialized intervention centres. Little is known about real-life outcome data in hospitals setting up this novel treatment and which favourable conditions are required for a continuous successful program. <b><i>Objectives:</i></b> In this study, we aim to evaluate the eligibility rate for BLVR and whether the implementation of BLVR in our academic hospital is feasible and yields clinically significant outcomes. <b><i>Method:</i></b> A retrospective evaluation of patients treated with EBV between January 2016 and August 2019 was conducted. COPD assessment test (CAT), forced expiratory volume in 1 s (FEV₁), residual volume (RV), and 6-min walking test (6MWT) were measured at baseline and 3 months after intervention. Paired sample <i>t</i> tests were performed to compare means before and after intervention. <b><i>Results:</i></b> Of 350 subjects screened, 283 (81%) were not suitable for intervention mostly due to lack of a target lobe. The remaining 67 subjects (19%) underwent bronchoscopic assessment, and if suitable, valves were placed in the same session. In total, 55 subjects (16%) were treated with EBV of which 10 did not have complete follow-up: 6 subjects had their valves removed because of severe pneumothorax (<i>n</i> = 2) or lack of benefit (<i>n</i> = 4) and the remaining 4 had missing follow-up data. Finally, 45 patients had complete follow-up at 3 months and showed an average change ± SD in CAT −4 ± 6 points, FEV₁ +190 ± 140 mL, RV −770 ± 790 mL, and +37 ± 65 m on the 6MWT (all <i>p</i> &#x3c; 0.001). After 1-year follow-up, 34 (76%) subjects had their EBV in situ. <b><i>Conclusion:</i></b> Implementing BLVR with EBV is feasible and effective. Only 16% of screened patients were eligible, indicating that this intervention is only applicable in a small subset of highly selected subjects with advanced emphysema, and therefore a high volume of COPD patients is essential for a sustainable BLVR program.

Late-Onset, Noninfectious Pulmonary Complications following Allogeneic Hematopoietic Stem Cell Transplantation: A Nationwide Cohort Study of Long-Term Survivors

<b><i>Background:</i></b> Survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk for pulmonary adverse events. Data on late-onset noninfectious pulmonary complications in long-term adult survivors of allo-HSCT are limited and incomplete. <b><i>Objectives:</i></b> This study aimed (1) to determine occurrence and degree of pulmonary sequelae in adult survivors of allo-HSCT and (2) to identify associations between pulmonary function, high-resolution CT (HRCT), and clinical characteristics. <b><i>Method:</i></b> In a nationwide, single-center cross-sectional study, 103 survivors (aged median [range] 35 [17–58] years, 53% females) were examined 17 (6–32) years after allo-HSCT and compared with healthy controls (<i>n</i> = 105). Methods included pulmonary function tests and HRCT. <b><i>Results:</i></b> Chronic graft-versus-host disease was diagnosed in 33% of survivors, including 12% with bronchiolitis obliterans syndrome (BOS). Mean lung volumes (TLC, FVC, and FEV₁) and gas diffusing capacity were &#x3e;80% of predicted for the survivors as a group, but significantly lower than in healthy controls. Pathological HRCT findings were detected in 48% of the survivors (71% airways disease, 35% interstitial lung disease, and 24% apical subpleural interstitial thickening). Air trapping (%) on HRCT correlated with % predicted FEV₁, <i>p</i> &#x3c; 0.001. In a multiple logistic regression model, both BOS and pathological findings on HRCT were associated with chemotherapy prior to allo-HSCT, <i>p</i> &#x3c; 0.05. <b><i>Conclusions:</i></b> Long-term allo-HSCT survivors had significantly lower pulmonary function than age- and gender-matched healthy controls and nearly half had pathological findings on HRCT. Longitudinal data will determine if pulmonary sequelae will remain stable or progress. We recommend lifelong monitoring of pulmonary function in allo-HSCT survivors. HRCT provides additional information, but is not suited for surveillance.

German S3 Guideline: Oxygen Therapy in the Acute Care of Adult Patients

<b><i>Background:</i></b> Oxygen (O₂) is a drug with specific biochemical and physiological properties, a range of effective doses and may have side effects. In 2015, 14% of over 55,000 hospital patients in the UK were using oxygen. 42% of patients received this supplemental oxygen without a valid prescription. Health care professionals are frequently uncertain about the relevance of hypoxemia and have low awareness about the risks of hyperoxemia. Numerous randomized controlled trials about targets of oxygen therapy have been published in recent years. A national guideline is urgently needed. <b><i>Methods:</i></b> A national S3 guideline was developed and published within the Program for National Disease Management Guidelines (AWMF) with participation of 10 medical associations. A literature search was performed until February 1, 2021, to answer 10 key questions. The Oxford Centre for Evidence-Based Medicine (CEBM) System (“The Oxford 2011 Levels of Evidence”) was used to classify types of studies in terms of validity. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used for assessing the quality of evidence and for grading guideline recommendation, and a formal consensus-building process was performed. <b><i>Results:</i></b> The guideline includes 34 evidence-based recommendations about indications, prescription, monitoring and discontinuation of oxygen therapy in acute care. The main indication for O₂ therapy is hypoxemia. In acute care both hypoxemia and hyperoxemia should be avoided. Hyperoxemia also seems to be associated with increased mortality, especially in patients with hypercapnia. The guideline provides recommended target oxygen saturation for acute medicine without differentiating between diagnoses. Target ranges for oxygen saturation are based depending on ventilation status risk for hypercapnia. The guideline provides an overview of available oxygen delivery systems and includes recommendations for their selection based on patient safety and comfort. <b><i>Conclusion:</i></b> This is the first national guideline on the use of oxygen in acute care. It addresses health care professionals using oxygen in acute out-of-hospital and in-hospital settings.

Clusters of Severe Eosinophilic Asthma in a Korean Asthma Cohort

<b><i>Background:</i></b> Targeted therapies have broadened the available treatment options for patients with severe eosinophilic asthma (SEA). However, differences in the magnitude of treatment responses among patients indicate the presence of various underlying pathophysiological processes and patient subgroups. <b><i>Objectives:</i></b> We aimed to describe the characteristics of SEA and identify its patient subgroups. <b><i>Methods:</i></b> Clinical data from the Cohort for Reality and Evolution of Adult Asthma in Korea were analyzed. Cluster analysis was performed among those with SEA using 5 variables, namely, prebronchodilator forced expiratory volume in 1 s, body mass index, age at symptom onset, smoking amount, and blood eosinophil counts. <b><i>Results:</i></b> Patients with SEA showed prevalent sensitization to aeroallergens, decreased lung function, and poor asthma control status. Cluster analysis revealed 3 distinctive subgroups among patients with SEA. Cluster 1 (<i>n</i> = 177) consisted of patients reporting the lowest blood eosinophils (median, 346.8 cells/μL) and modest severe asthma with preserved lung function during the 12-month treatment period. Cluster 2 (<i>n</i> = 42) predominantly included smoking males with severe persistent airway obstruction and moderate eosinophilia (median, 451.8 cells/μL). Lastly, cluster 3 (<i>n</i> = 95) included patients with the most severe asthma, the highest eosinophil levels (median, 817.5 cells/μL), and good treatment response in terms of improved lung function and control status. <b><i>Conclusions:</i></b> Three subgroups were identified in SEA through the cluster analysis. The distinctive features of each cluster may help physicians predict patients who will respond to biologics with greater magnitude of clinical improvement. Further research regarding the underlying pathophysiology and clinical importance of each subgroup is warranted.

Autologous Blood Patch Pleurodesis for the Management of a Persistent Air Leak after Secondary Spontaneous Pneumothorax

Patients with secondary spontaneous pneumothorax (SSP) complicated by persistent air leak (PAL) and who are poor surgical candidates have limited treatment options. This case series explored autologous blood patch pleurodesis as a possible cost-effective management option. A total of 46 episodes of SSP with PAL were included. The procedure was successful in 33 (71.7%). Of these, 17 (51.5%) resolved within 1 day. The mean duration of intercostal drainage prior to the blood patch was 22 days in the successful group. Pneumothoraces with incomplete lung re-expansion at the time of procedure were successful in 20 of 30 (66.7%). Only human immunodeficiency virus infection was associated with failure (<i>p</i> = 0.03). Adverse events included transient fever (<i>n</i> = 3) that resolved spontaneously, and empyema (<i>n</i> = 3) which were successfully managed with antibiotics and pigtail drainage. We conclude that a large proportion of patients with SSP complicated by PAL who are unfit for surgery may be liberated from intercostal drainage by an autologous blood patch pleurodesis, with minimal adverse effects.

Nontuberculous Mycobacteria under Scrutiny in the Geneva Area (2015–2020)

<b><i>Background:</i></b> Nontuberculous mycobacteria (NTM) are increasingly identified in industrialized countries, and their role as pathogens is more frequently recognized. The relative prevalence of NTM strains shows an important geographical variability. Thus, establishing the local relative prevalence of NTM strains is relevant and useful for clinicians. <b><i>Methods:</i></b> Retrospective analysis (2015–2020) of a comprehensive database was conducted including all results of cultures for mycobacteria in a University Hospital (Geneva, Switzerland), covering a population of approximately 500,000 inhabitants. All NTM culture-positive patients were included in the analyses. Patients’ characteristics, NTM strains, and time to culture positivity were reported. <b><i>Results:</i></b> Among 38,065 samples analyzed during the study period, 411 were culture-positive for NTM, representing 236 strains, and 231 episodes of care which occurred in 222 patients. Patients in whom NTM were identified were predominantly female (55%), with a median age of 62 years, and a low BMI (median: 22.6 kg/m²). The <i>Mycobacterium avium</i> complex (MAC) was the most frequently identified group (37% of strains) followed by <i>Mycobacterium gordonae</i> (25%) and <i>Mycobacterium xenopi</i> (12%) among the slowly growing mycobacteria (SGM), while the <i>Mycobacterium chelonae/abscessus</i> group (11%) were the most frequently identified rapidly growing mycobacteria (RGM). Only 19% of all patients were treated, mostly for pulmonary infections: the MAC was the most frequently treated NTM (<i>n</i> = 19, 43% of cases in patients treated) followed by RGM (<i>n</i> = 15, 34%) and <i>M. xenopi</i> (<i>n</i> = 6, 14%). Among those treated, 23% were immunosuppressed, 12% had pulmonary comorbidities, and 5% systemic comorbidities. Cultures became positive after a median of 41 days (IQR: 23; 68) for SGM and 28 days (14; 35) for RGM. <b><i>Conclusions:</i></b> In Western Switzerland, <i>M. avium</i> and <i>M. gordonae</i> were the most prevalent NTM identified. Positive cultures for NTM led to a specific treatment in 19% of subjects. Patients with a positive culture for NTM were mostly female, with a median age of 62 years, a low BMI, and a low prevalence of immunosuppression or associated severe comorbidities.

Treatment of Sleep Apnea with Positive Airway Pressure and Its Association with Diastolic Dysfunction: A Systematic Review and Meta-Analysis

<b><i>Background:</i></b> This meta-analysis assessed the effect of long-term (&#x3e;6 weeks) noninvasive positive airway pressure (PAP) on diastolic function in patients with obstructive sleep apnea (OSA). <b><i>Methods:</i></b> We searched the databases for randomized clinical trials including Ovid MEDLINE, Ovid Embase Scopus, Web of Science, Google Scholar, and EBSCO CINAHL from inception up to December 20, 2019. The search was not restricted to time, publication status, or language. Two independent investigators screened the studies and extracted the data, in duplicate. Risk of bias was assessed using Cochrane collaboration tools. <b><i>Results:</i></b> A total of 2,753 abstracts were resulted from literature search. A total of 9 randomized clinical trials assessing the effect of long-term (&#x3e;6 weeks) PAP on diastolic function in patients with OSA including 833 participants were included. The following echo parameters were found in treated patients: a decrease in deceleration time (−39.49 ms CI [−57.24, −21.74]; <i>p</i> = 0.000), isovolumic relaxation time (−9.32 ms CI [−17.08, −1.57]; <i>p</i> = 0.02), and the ratio of early mitral inflow velocity to mitral annular early diastolic velocity (−1.38 CI [−2.6, −0.16]; <i>p</i> = 0.03). However, changes in left-atrial volume index and the ratio of early to late mitral inflow velocities were not statistically different. The risk of bias was mild to moderate among the studies. <b><i>Conclusion:</i></b> Our results suggest that chronic treatment of moderate to severe OSA with noninvasive PAP is associated with improvement in echocardiographic findings of diastolic dysfunction.