Exercise capacity and physical activity in COPD patients treated with a LAMA/LABA combination: a systematic review and meta-analysis.

BACKGROUND: Persistent airflow limitation and dyspnoea may reduce chronic obstructive pulmonary disease (COPD) patients exercise capacity and physical activity, undermining their physical status and quality of life. Long-acting muscarinic antagonists and long-acting beta-2 agonists (LAMA/LABA) combinations are amongst moderate-to-severe COPD recommended treatments. This article analyses LAMA/LABA combinations effect on COPD patients exercise capacity and physical activity outcomes. METHODS: A systematic review and meta-analysis of double-blind randomized controlled trials comparing LAMA/LABA combinations against monotherapy or placebo was conducted. RESULTS: Seventeen articles were identified (N = 4041 patients). In endurance shuttle walk test and constant work rate cycle ergometry, LAMA/LABA combinations obtained better results than placebo, but not monotherapy, whereas in 6-min walking test, results favoured LAMA/LABA over monotherapy (four studies), but not over placebo (one study). Moreover, LAMA/LABA combinations obtained better results than placebo in number of steps per day, reduction in percentage of inactive patients and daily activity-related energy expenditure, and better than monotherapy when measuring time spent on ≥ 1.0-1.5, ≥ 2.0 and ≥ 3.0 metabolic equivalents of task activities. CONCLUSIONS: LAMA/LABA combinations in COPD patients provided better results than monotherapy or placebo in most exercise capacity and physical activity outcomes.

Efficacy of Low-Dose versus High-Dose Continuous Cyclic Azithromycin Therapy for Preventing Acute Exacerbations of COPD.

BACKGROUND: Long-term azithromycin therapy significantly reduces the frequency of COPD exacerbations (ECOPD). However, previous studies have used different dosing regimens, and the efficacy of these regimens has not been compared. OBJECTIVE: Compare the efficacy of low-dose with high-dose continuous cyclic azithromycin (CC-A) in severe COPD. METHODS: Patients with severe COPD and repeated exacerbations (ECOPD ≥4 or ≥3 with at least 1 hospital admission in the previous year) were prospectively recruited (January 2017 to December 2019) as a multicenter cohort (from 3 university hospitals in the Barcelona area) and treated with low-dose CC-A: 250 mg 3 times per week (250-CC-A group). This cohort was compared with a historical (January 2007 to December 2013) single-center cohort of severe COPD with frequent ECOPD treated with high-dose CC-A: 500 mg 3 times per week (500-CC-A group). To assess differences in ECOPD prevention according to the administration of low-dose or high-dose CC-A, moderate-to-severe ECOPD was evaluated during the 12-month period before and after starting CC-A therapy. RESULTS: Fifty-eight patients with severe COPD were evaluated: 37 in the low-dose group and 21 in the high-dose group. The 250-CC-A therapy group achieved a mean reduction in moderate-to-severe ECOPD of 65.6% at 12 months after starting CC-A therapy (with a 61.5% reduction in hospitalizations), while the 500-CC-A group achieved a reduction of 60.5% (with a 44.8% reduction in hospitalizations). No significant differences between 250-CC-A and 500-CC-A dosages were observed in the mean annual reduction of moderate-to-severe ECOPD (p = 0.55) or hospitalizations (p = 0.07) with respect to the year prior to starting CC-A. CONCLUSIONS: Low-dose 250-CC-A therapy over a 1-year period is similar to high-dose 500-CC-A in reducing exacerbation frequency in severe COPD patients with frequent ECOPD despite maximal medical therapy.

A step-down protocol for omalizumab treatment in oral corticosteroid-dependent allergic asthma patients.

AIMS: There are no specific criteria for a step-down or withdrawal dose of omalizumab (OMA). Our purpose was to evaluate the viability of a protocol for OMAlizumab DOse REduction (the OMADORE study) in severe allergic asthma (SAA). METHODS: The study population included 35 SAA patients treated during a minimum period of 1 year with oral corticosteroids (OC) equivalent to a mean daily dose of 4 mg of methyl-prednisolone. To qualify for the protocol, the patients had to have received treatment with OMA for at least one and a half years, OC dose had to have reached the lowest tolerated dose and spirometry had to be greater than or equal to that at entry. The interventions were (a) OMA dose was reduced by half; (b) if patients were clinically stable after 6 months, the dose was halved again; (c) if repeated OC boosters were needed and/or spirometry worsened by more than 10%, OMA dose was raised to the previous figure until stabilization. RESULTS: Mean age was 52.5 (17) years, median monthly OC dose was 120 (IQR: 225) mg. Pulmonary function: FVC: 79.7 (20.2)%; FEV1 : 64.8 (21.7)%; FEV1 / FVC: 61.7(13.8)%. OMA could be withdrawn in 34.3% of the patients; 22.9% tolerated a reduction, and in 42.9% the dose could not be modified. Follow-up time after reduction or withdrawal ranged from 12 to 30 months. There were no severe exacerbations requiring emergency assistance or admission. CONCLUSIONS: The OMADORE study found that in more than 50% of SAA patients on OC, OMA dose can be safely reduced or withdrawn based on a progressive dose reduction protocol.

The respiratory microbiome in bronchial mucosa and secretions from severe IgE-mediated asthma patients.

BACKGROUND: The bronchial microbiome in chronic lung diseases presents an abnormal pattern, but its microbial composition and regional differences in severe asthma have not been sufficiently addressed. The aim of the study was to describe the bacterial community in bronchial mucosa and secretions of patients with severe chronic asthma chronically treated with corticosteroids in addition to usual care according to Global Initiative for Asthma. Bacterial community composition was obtained by 16S rRNA gene amplification and sequencing, and functional capabilities through PICRUSt. RESULTS: Thirteen patients with severe asthma were included and provided 11 bronchial biopsies (BB) and 12 bronchial aspirates (BA) suitable for sequence analyses. Bacteroidetes, Firmicutes, Proteobacteria and Actinobacteria showed relative abundances (RAs) over 5% in BB, a cutoff that was reached by Streptococcus and Prevotella at genus level. Legionella genus attained a median RA of 2.7 (interquartile range 1.1-4.7) in BB samples. In BA a higher RA of Fusobacteria was found, when compared with BB [8.7 (5.9-11.4) vs 4.2 (0.8-7.5), p = 0.037], while the RA of Proteobacteria was lower in BA [4.3 (3.7-6.5) vs 17.1 (11.2-33.4), p = 0.005]. RA of the Legionella genus was also significantly lower in BA [0.004 (0.001-0.02) vs. 2.7 (1.1-4.7), p = 0.005]. Beta-diversity analysis confirmed the differences between the microbial communities in BA and BB (R2 = 0.20, p = 0.001, Adonis test), and functional analysis revealed also statistically significant differences between both types of sample on Metabolism, Cellular processes, Human diseases, Organismal systems and Genetic information processing pathways. CONCLUSIONS: The microbiota in the bronchial mucosa of severe asthma has a specific pattern that is not accurately represented in bronchial secretions, which must be considered a different niche of bacteria growth.

Effectiveness of a Respiratory Day Hospital Program to Reduce Admissions for Exacerbation in Patients with Severe COPD: A Prospective, Multicenter Study.

The respiratory Day Hospital (DH) is a care facility currently operating at various healthcare institutions. It monitors patients with severe chronic obstructive pulmonary disease (COPD) presenting repeated exacerbations with at least two hospital admissions per year. The main aim of the study was to evaluate the effectiveness of the DH program for controlling admissions for COPD exacerbations in this cohort of patients, and to identify clinical factors associated with hospitalizations and mortality. An observational prospective multicenter study was carried out at three hospitals. The sample comprised 150 consecutive patients (median age 70 [65-76] years, FEV1 33 [26-43]%, 97% males), included at the DH program. Over a one-year period, variables assessing effectiveness and use of healthcare resources were recorded. Factors associated with hospitalizations and mortality were identified. Patients made a median of 4[2-5] emergency visits due to COPD exacerbations with a median of 1[0-2] hospitalization(s)/year. Most of exacerbations (77%) were evaluated at the DH, but there were fewer hospitalizations from the DH than from the emergency department (21% vs. 81%, p < 0.001). In all, 29% of the patients had at least two admissions; these were the patients with the most severe disease. Age, readmission at 30-days and the presence of respiratory failure were the predictors of mortality. In conclusion, the DH program is an effective model for reducing hospitalizations in this cohort of patients. In all, 29% of the patients required two hospital admissions or more; these patients had more advanced disease and poorer prognosis, and would be most likely to benefit from additional care support.

Omalizumab Is Equally Effective in Persistent Allergic Oral Corticosteroid-Dependent Asthma Caused by Either Seasonal or Perennial Allergens: A Pilot Study.

Omalizumab is marketed for chronic severe asthma patients who are allergic to perennial allergens. Our purpose was to investigate whether omalizumab is also effective in persistent severe asthma due to seasonal allergens. Thirty patients with oral corticosteroid-dependent asthma were treated with Omalizumab according to the dosing table. For each patient with asthma due to seasonal allergens, we recruited the next two consecutive patients with asthma due to perennial allergens. The dose of oral methyl prednisolone was tapered at a rate of 2 mg every two weeks after the start of treatment with omalizumab depending on tolerance. At each monthly visit, a forced spirometry and fractional exhaled nitric oxide (FeNO) measurement were performed and the accumulated monthly methyl prednisolone dose was calculated. At entry, there were no differences between groups in terms of gender, body mass index or obesity, year exacerbation rate, monthly dose of methyl-prednisolone (MP), FeNO and blood immunoglobuline E (IgE) MP, FeNO and IgE values, or spirometry (perennial: FVC: 76%; FEV1: 62%; seasonal: FVC: 79%; FEV1: 70%). The follow-up lasted 76 weeks. One patient in each group was considered a non-responder. Spirometry did not worsen in either group. There was a significant intragroup reduction in annual exacerbation rate and methyl prednisolone consumption but no differences were detected in the intergroup comparison. Omalizumab offered the same clinical benefits in the two cohorts regardless of whether the asthma was caused by a seasonal or a perennial allergen. These results strongly suggest that allergens are the trigger in chronic asthma but that it is the persistent exposure to IgE that causes the chronicity.

Emergency Hospital Care for Exacerbation of COPD: Is Inhaled Maintenance Therapy Modified?

BACKGROUND: The impact of hospital emergency care and inward admission for acute exacerbations of COPD on inhaled maintenance treatment is not well known. OBJECTIVE: Therefore, we evaluated the impact of short-stay emergency hospital care and inward admission for acute exacerbation of COPD (eCOPD) on inhaled maintenance treatment prescribed at discharge. DESIGN: Prospective observational cohort study of patients presenting with eCOPD at emergency departments in 16 hospitals of the Spanish healthcare system. The ethics committee at each hospital approved the study and patients provided an informed consent before inclusion. We classified the patients according to the severity of COPD: mild/moderate (FEV1 ≥ 50% predicted) or severe/very severe (FEV1 < 50% predicted) and need of inward hospitalisation. We analysed changes to maintenance treatment on discharge according to GOLD strategy. RESULTS: 1559 patients, 65% required hospitalisation. The most common maintenance treatment was inhaled corticoids (ICS) (80.9%) followed by long-acting beta-agonists (LABA) (75.4%). The most common combination was triple therapy (LABA+ LAMA+ICS) (56.2%) followed by LABA+ICS dual therapy (18.2%) regardless of the severity of COPD. In more than 60% of patients treatment was not changed at discharge. The most common change in treatment was a reduction when discharge was from emergency care and an increase after hospitalisation (-21.6% and +19.5% in severe/very severe COPD, respectively). CONCLUSIONS: Emergency hospital care for eCOPD does not usually induce changes in inhaled maintenance treatment for COPD regardless of the duration of the hospital stay.

Roflumilast added to triple therapy in patients with severe COPD: a real life study.

BACKGROUND: Roflumilast is used in severe chronic obstructive pulmonary disease (COPD) patients with frequent exacerbations. However, limited information is available on its impact in a "real-life" population that may be receiving triple therapy. OBJECTIVE: This study aimed to evaluate the effectiveness and safety of roflumilast in COPD patients already receiving triple therapy (long-acting ß-agonist/inhaled corticosteroids and long-acting muscarinic antagonist). METHODS: Prospective registry that included COPD patients who were prescribed roflumilast added to triple therapy. The yearly rate of all COPD exacerbations before and after roflumilast and side effects related to the drug were registered. RESULTS: Among 55 patients prescribed 500 mg of roflumilast. Only 50.9% (n = 28) completed 1 year of therapy (roflumilast group). A reduction of all exacerbations with roflumilast was observed (2.75 ± 0.29 vs. 3.57 ± 0.26; P = 0.022), with a particular benefit in patients with ≥4 exacerbations prior to initiating therapy (3.55 ± 0.51 vs. 5.00 ± 0.30; P = 0.034). Side effects (mainly gastrointestinal) and treatment discontinuation occurred in 69.1% and 49.1% of the overall population, respectively. CONCLUSIONS: Roflumilast, when added to triple therapy, reduces exacerbations in a "real-life" population of severe COPD patients with frequent exacerbations. However, side effects are more common and lead more frequently to discontinuation of therapy than has been reported in trials.

Severity-related changes of bronchial microbiome in chronic obstructive pulmonary disease.

Bronchial colonization by potentially pathogenic microorganisms (PPMs) is often demonstrated in chronic obstructive pulmonary disease (COPD), but culture-based techniques identify only a portion of the bacteria in mucosal surfaces. The aim of the study was to determine changes in the bronchial microbiome of COPD associated with the severity of the disease. The bronchial microbiome of COPD patients was analyzed by 16S rRNA gene amplification and pyrosequencing in sputum samples obtained during stable disease. Seventeen COPD patients were studied (forced expiratory volume in the first second expressed as a percentage of the forced vital capacity [FEV1%] median, 35.0%; interquartile range [IQR], 31.5 to 52.0), providing a mean of 4,493 (standard deviation [SD], 2,598) sequences corresponding to 47 operational taxonomic units (OTUs) (SD, 17) at a 97% identity level. Patients were dichotomized according to their lung function as moderate to severe when their FEV1% values were over the median and as advanced when FEV1% values were lower. The most prevalent phyla in sputum were Proteobacteria (44%) and Firmicutes (16%), followed by Actinobacteria (13%). A greater microbial diversity was found in patients with moderate-to-severe disease, and alpha diversity showed a statistically significant decrease in patients with advanced disease when assessed by Shannon (ρ = 0.528; P = 0.029, Spearman correlation coefficient) and Chao1 (ρ = 0.53; P = 0.028, Spearman correlation coefficient) alpha-diversity indexes. The higher severity that characterizes advanced COPD is paralleled by a decrease in the diversity of the bronchial microbiome, with a loss of part of the resident flora that is replaced by a more restricted microbiota that includes PPMs.

Pseudomonas aeruginosa isolates in severe chronic obstructive pulmonary disease: characterization and risk factors.

BACKGROUND: Patients with severe chronic obstructive pulmonary disease (COPD) are at increased risk of infection by P. aeruginosa. The specific role of bronchiectasis in both infection and chronic colonization by this microorganism in COPD, however, remains ill defined.To evaluate the prevalence and risk factors for P. aeruginosa recovery from sputum in outpatients with severe COPD, characterizing P. aeruginosa isolates by pulsed-field gel electrophoresis (PFGE) and focusing on the influence of bronchiectasis on chronic colonization in these patients. METHODS: A case-cohort study of 118 patients with severe COPD attended at a Respiratory Day Unit for an acute infectious exacerbation and followed up over one year. High-resolution CT scans were performed during stability for bronchiectasis assessment and sputum cultures were obtained during exacerbation and stability in all patients. P. aeruginosa isolates were genotyped by PFGE. Determinants of the recovery of P. aeruginosa in sputum and chronic colonization by this microorganism were assessed by multivariate analysis. RESULTS: P. aeruginosa was isolated from 41 of the 118 patients studied (34.7%). Five of these 41 patients (12.2%) with P. aeruginosa recovery fulfilled criteria for chronic colonization. In the multivariate analysis, the extent of bronchiectasis (OR 9.8, 95% CI: 1.7 to 54.8) and the number of antibiotic courses (OR 1.7, 95% CI: 1.1 to 2.5) were independently associated with an increased risk of P. aeruginosa isolation. Chronic colonization was unrelated to the presence of bronchiectasis (p=0.75). In patients with chronic colonization the isolates of P. aeruginosa retrieved corresponded to the same clones during the follow-up, and most of the multidrug resistant isolates (19/21) were harbored by these patients. CONCLUSIONS: The main risk factors for P. aeruginosa isolation in severe COPD were the extent of bronchiectasis and exposure to antibiotics. Over 10% of these patients fulfilled criteria for chronic colonization by P. aeruginosa and showed clonal persistence, independently of the presence of bronchiectasis.

Effect of dynamic random leaks on the monitoring accuracy of home mechanical ventilators: a bench study.

BACKGROUND: So far, the accuracy of tidal volume (VT) and leak measures provided by the built-in software of commercial home ventilators has only been tested using bench linear models with fixed calibrated and continuous leaks. The objective was to assess the reliability of the estimation of tidal volume (VT) and unintentional leaks in a single tubing bench model which introduces random dynamic leaks during inspiratory or expiratory phases. METHODS: The built-in software of four commercial home ventilators and a fifth ventilator-independent ad hoc designed external software tool were tested with two levels of leaks and two different models with excess leaks (inspiration or expiration). The external software analyzed separately the inspiratory and expiratory unintentional leaks. RESULTS: In basal condition, all ventilators but one underestimated tidal volume with values ranging between -1.5 ± 3.3% to -8.7% ± 3.27%. In the model with excess of inspiratory leaks, VT was overestimated by all four commercial software tools, with values ranging from 18.27 ± 7.05% to 35.92 ± 17.7%, whereas the ventilator independent-software gave a smaller difference (3.03 ± 2.6%). Leaks were underestimated by two applications with values of -11.47 ± 6.32 and -5.9 ± 0.52 L/min. With expiratory leaks, VT was overestimated by the software of one ventilator and the ventilator-independent software and significantly underestimated by the other three, with deviations ranging from +10.94 ± 7.1 to -48 ± 23.08%. The four commercial tools tested overestimated unintentional leaks, with values between 2.19 ± 0.85 to 3.08 ± 0.43 L/min. CONCLUSIONS: In a bench model, the presence of unintentional random leaks may be a source of error in the measurement of VT and leaks provided by the software of home ventilators. Analyzing leaks during inspiration and expiration separately may reduce this source of error.

What Circuits, Masks and Filters Should Be Used in Home Non-Invasive Mechanical Ventilation.

Most of the published reviews about non-invasive home ventilation mainly reflect the technical aspects of ventilators. There is much less information about the consumables most used at home. However, the choice of a good interface or tubing system can lead to physiological changes in the patient-ventilator interaction that the clinician should be aware of. These physiological changes may affect the performance of the ventilator itself, the reliability of monitoring and, of course, the comfort of the patient. The use of different circuits, masks or filters is therefore related to the concepts of rebreathing, compressible volume, instrumental dead space or leak estimation and tidal volume. Through certain bench experiments, it is possible to determine the implications that each of these elements may have in clinical practice.

Systemic and functional effects of continuous azithromycin treatment in patients with severe chronic obstructive pulmonary disease and frequent exacerbations.

Background: Continuous treatment with azithromycin may lead to fewer acute exacerbations of chronic obstructive pulmonary disease (AECOPD), but little is known of its impact on systemic and functional outcomes in real-life settings. Methods: This was a multicenter prospective observational study of patients with severe COPD who started treatment with azithromycin. Tests were compared at baseline and after 3 and 12 months of treatment. These included lung function tests, a 6-min walking test (6MWT), and enzyme-linked immunosorbent assays of serum and sputum markers, such as interleukins (IL-6, IL-8, IL-13, IL-5), tumor necrosis factor receptor 2 (TNFR2), and inflammatory markers. Incidence rate ratios (IRR) and their 95% confidence intervals (95% CI) are reported. Results: Of the 478 eligible patients, the 42 who started azithromycin experienced reductions in AECOPDs (IRR, 0.34; 95% CI, 0.26-0.45) and hospitalizations (IRR, 0.39; 95% CI, 0.28-0.49). Treatment was also associated with significant improvement in the partial arterial pressure of oxygen (9.2 mmHg, 95% CI 1.4-16.9) at 12 months. While TNFR2 was reduced significantly in both serum and sputum samples, IL-13 and IL-6 were only significantly reduced in serum samples. Moreover, an elevated serum and sputum IL-8 level significantly predicted good clinical response to treatment. Conclusion: Continuous azithromycin treatment in a cohort of patients with severe COPD and frequent exacerbations can significantly reduce the number and severity of exacerbations and improve gas exchange. Treatment changes the pattern of microorganism isolates and decreases the inflammatory response. Of note, IL-8 may have utility as a predictor of clinical response to azithromycin treatment.

Genetic Adaptation and Acquisition of Macrolide Resistance in Haemophilus spp. during Persistent Respiratory Tract Colonization in Chronic Obstructive Pulmonary Disease (COPD) Patients Receiving Long-Term Azithromycin Treatment.

Patients with chronic obstructive pulmonary disease (COPD) benefit from the immunomodulatory effect of azithromycin, but long-term administration may alter colonizing bacteria. Our goal was to identify changes in Haemophilus influenzae and Haemophilus parainfluenzae during azithromycin treatment. Fifteen patients were followed while receiving prolonged azithromycin treatment (Hospital Universitari de Bellvitge, Spain). Four patients (P02, P08, P11, and P13) were persistently colonized by H. influenzae for at least 3 months and two (P04 and P11) by H. parainfluenzae. Isolates from these patients (53 H. influenzae and 18 H. parainfluenzae) were included to identify, by whole-genome sequencing, antimicrobial resistance changes and genetic variation accumulated during persistent colonization. All persistent lineages isolated before treatment were azithromycin-susceptible but developed resistance within the first months, apart from those belonging to P02, who discontinued the treatment. H. influenzae isolates from P08-ST107 acquired mutations in 23S rRNA, and those from P11-ST2480 and P13-ST165 had changes in L4 and L22. In H. parainfluenzae, P04 persistent isolates acquired changes in rlmC, and P11 carried genes encoding MefE/MsrD efflux pumps in an integrative conjugative element, which was also identified in H. influenzae P11-ST147. Other genetic variation occurred in genes associated with cell wall and inorganic ion metabolism. Persistent H. influenzae strains all showed changes in licA and hgpB genes. Other genes (lex1, lic3A, hgpC, and fadL) had variation in multiple lineages. Furthermore, persistent strains showed loss, acquisition, or genetic changes in prophage-associated regions. Long-term azithromycin therapy results in macrolide resistance, as well as genetic changes that likely favor bacterial adaptation during persistent respiratory colonization. IMPORTANCE The immunomodulatory properties of azithromycin reduce the frequency of exacerbations and improve the quality of life of COPD patients. However, long-term administration may alter the respiratory microbiota, such as Haemophilus influenzae, an opportunistic respiratory colonizing bacteria that play an important role in exacerbations. This study contributes to a better understanding of COPD progression by characterizing the clinical evolution of H. influenzae in a cohort of patients with prolonged azithromycin treatment. The emergence of macrolide resistance during the first months, combined with the role of Haemophilus parainfluenzae as a reservoir and source of resistance dissemination, is a cause for concern that may lead to therapeutic failure. Furthermore, genetic variations in cell wall and inorganic ion metabolism coding genes likely favor bacterial adaptation to host selective pressures. Therefore, the bacterial pathoadaptive evolution in these severe COPD patients raise our awareness of the possible spread of macrolide resistance and selection of host-adapted clones.

Critical appraisal of international adult bronchiectasis guidelines using the AGREE II tool.

BACKGROUND: Guidelines aim to standardize and optimize diagnosis and management. We evaluated the quality of evidence supporting recommendations from different international adult guidelines on bronchiectasis, and classified with the GRADE system. METHODS: Quality of eligible clinical practice guidelines was assessed for six domains using the AGREE II tool, with ≥ 80% rating as excellent. RESULTS: Seven guidelines (283 recommendations) were analyzed, and four of them were considered "recommended for use" (three reported after 2017 as excellent). Overall, 144 (50.9%) recommendations were based on low-quality evidence, representing 81.5% in diagnosis and 36.2% in therapy. In contrast, 5/92 (5.4%) and 40/191 (20.9%) recommendations regarding diagnostic and treatment (respectively) were based on high-quality evidence. Quality agreement ratings were significantly (p< 0.05) higher for guidelines delivered after 2015, progressing from 27.7% to 58.3%, qualifying as excellent. Highest scores were documented in the domains of "scope and purpose" followed by "clarifying of presentation" and "editorial independence". CONCLUSION: Updated guidelines reported after 2017 improved quality, although well-designed randomized clinical trials remain an unmet need. AGREE II quality assessment identified four guidelines qualified as recommended for use. Improvements are required in stakeholder involvement and applicability.

Pulmonologists' Opinion on the Use of Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease Patients in Spain: A Cross-Sectional Survey.

Introduction: Identifying the variables that guide decision-making in relation to the use of inhaled corticosteroids (ICS) can contribute to the appropriate use of these drugs. The objective of this study was to identify the clinical variables that physicians consider most relevant for prescribing or withdrawing ICS in COPD. Methods: A cross-sectional survey was conducted in Spain from November 2020 to May 2021. Therapeutic decisions on the use of ICS in 11 hypothetical COPD patient profiles were collected using an online survey answered by specialists with experience in the management of patients with COPD. Mixed-effects logistic regression was used to analyze the impact of patients' characteristics in the therapeutic decision for prescribing ICS or proceeding to its withdrawal. Results: A total of 74 pulmonologists agreed to collaborate in the survey and answered the questionnaire. The results showed great variability, with only 2 profiles achieving consensus for starting or withdrawing the treatment. The frequency and severity of exacerbations influenced the decision to prescribe ICS in a dose-response fashion (1 exacerbation odds ratio (OR) = 1.86, 95% confidence interval (CI) 1.02 to 3.43, two exacerbations OR = 11.6, 95% CI: 4.47 to 30.2 and three OR = 123, 95% CI: 25 to 601). Similarly, increasing blood eosinophils and history of asthma were associated with ICS use. On the other hand, pneumonia reduced the probability of initiating treatment with ICS (OR = 0.54 [0.29 to 0.98]). Lung function and dyspnea degree did not influence the clinician's therapeutic decision. The results for withdrawal of ICS were similar but in the opposite direction. Conclusion: In accordance with guidelines, exacerbations, blood eosinophils and history of asthma or pneumonia are the factors considered by pulmonologist for the indication or withdrawal of ICS. However, the agreement in prescription or withdrawal of ICS when confronted with hypothetical cases is very low, suggesting a great variability in clinical practice.

Dual Monoclonal Antibody Therapy for a Severe Asthma Patient.

INTRODUCTION: Omalizumab, the first biological treatment for severe allergic bronchial asthma, has been on the market for more than a decade. Omalizumab was initially considered to be an IgE-blocking agent, and therefore, an inhibitor of the Th2 (allergic or adaptive) cascade. More recently, other monoclonal antibodies for severe eosinophilic asthma have become available, which exert an anti-eosinophilic effect basically by blocking IL5 or its receptor. These agents exert this effect regardless of the origin of the eosinophils (i.e., the adaptive or the innate immune system). CASE STUDY: An oral corticosteroid-dependent allergic asthma patient was treated with omalizumab. After a year of treatment, the improvement remained very limited and the medical team proposed discontinuation. However, the patient felt that her asthma had improved and she refused to give up the therapy, which continued for ten years. The mean accumulated oral corticosteroid dose per month during the last year was around 200 mg; despite this, the FEV1 was low, Since the patient had a high number of eosinophils in peripheral blood, she accepted a switch to mepolizumab when this agent became available. One year later, the clinical improvement was limited and severe symptoms of allergy reappeared, and a combination of monoclonal antiobodies (omalizumab and mepolizumab) was proposed. RESULTS: After 24 months of dual therapy, a marked improvement in the FEV1 was observed, reaching the normal range, and the OC dose was reduced to 2.5 mg per day of prednisolone. No side effects were observed. CONCLUSIONS: In some severe allergic asthma patients with persistently high eosinophil counts in peripheral blood and who are considered non- or mild responders to anti-IgE and anti-IL5 administered individually, a combination of the two antibodies covering the entire T2 spectrum may be effective.

The Respiratory Microbiome in Cystic Fibrosis: Compartment Patterns and Clinical Relationships in Early Stage Disease.

We compared the bacterial microbiomes lodged in the bronchial tree, oropharynx and nose of patients with early stage cystic fibrosis (CF) not using chronic antibiotics, determining their relationships with lung function and exacerbation frequency. CF patients were enrolled in a cohort study during stability and were checked regularly over the following 9 months. Upper respiratory samples (sputum [S], oropharyngeal swab [OP] and nasal washing [N]) were collected at the first visit and every 3 months. 16S rRNA gene amplification and sequencing was performed and analyzed with QIIME. Seventeen CF patients were enrolled (16.6 SD 9.6 years). Alpha-diversity of bacterial communities between samples was significantly higher in S than in OP (Shannon index median 4.6 [IQR: 4.1-4.9] vs. 3.7 [IQR: 3-1-4.1], p = 0.003/Chao 1 richness estimator median 97.75 [IQR: 85.1-110.9] vs. 43.9 [IQR: 31.7-59.9], p = 0.003) and beta-diversity analysis also showed significant differences in the microbial composition of both respiratory compartments (Adonis test of Bray Curtis dissimilarity matrix, p = 0.001). Dominant taxa were found at baseline in five patients (29.4%), who showed lower forced expiratory volume in the first second (FEV1%, mean 74.8 [SD 19] vs. 97.2 [SD 17.8], p = 0.035, Student t test). The Staphylococcus genus had low RAs in most samples (median 0.26% [IQR 0.01-0.69%]), but patients with RA > 0.26% of Staphylococcus in bronchial secretions suffered more exacerbations during follow-up (median 2 [IQR 1-2.25] vs. 0 [0-1], p = 0.026. Mann-Whitney U test), due to S. aureus in more than a half of the cases, microorganism that often persists as bronchial colonized in these patients (9/10 [90%] vs. 2/7 [28.6%], p = 0.034, Fisher's exact test). In conclusion, the bronchial microbiome had significantly higher diversity than the microbial flora lodged in the oropharynx in early stage CF. Although the RA of the Staphylococcus genus was low in bronchial secretions and did not reach a dominance pattern, slight overrepresentations of this genus was associated with higher exacerbation frequencies in these patients.

[Causes of death and risk factors for mortality in patients with severe chronic obstructive pulmonary disease]. / Causas de muerte en pacientes con EPOC grave. Factores pronósticos.

OBJECTIVE: The objective of this study was to assess the causes of death and risk factors for mortality in a cohort of patients with severe chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: We studied 203 patients with severe COPD (forced expiratory volume in 1 second [FEV(1)] <50%), who were attended in our respiratory department day hospital (2001-2006). Clinical variables were recorded on inclusion, and clinical course and causes of death were retrospectively reviewed. RESULTS: The mean (SD) age of patients was 69 (8) years and the mean FEV(1) was 30.8% (8.2%). One-hundred and nine patients died (53.7%); death was attributed to respiratory causes in 72 (80.9%), with COPD exacerbation being the most frequent specific cause within this category (48.3%). During follow-up, 18.7% required admission to the intensive care unit (ICU). Survival at 1, 3, and 5 years was 80%, 53%, and 26%, respectively. The multivariate analysis showed that mortality was associated with age, stage IV classification according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), cor pulmonale, and hospital admission during the year prior to inclusion. Need for admission to the ICU during follow-up was a factor independently associated with higher mortality. CONCLUSIONS: Mortality in patients with severe COPD was high and exacerbation of the disease was one of the most frequent causes of death. Age, GOLD stage, cor pulmonale, prior admission to hospital, and need for admission to the ICU during follow-up were independent predictors of mortality.