Incidence and profile of severe exacerbations of chronic obstructive pulmonary disease due to biomass smoke or tobacco.

INTRODUCTION AND OBJECTIVES: Stable chronic obstructive pulmonary disease (COPD) caused by biomass smoke (B-COPD) has some differences from tobacco-induced-COPD (T-COPD), but acute exacerbations (AECOPD) have not been well characterized in B-COPD. OBJECTIVE: To compare the incidence, characteristics and outcomes of AECOPD in B-COPD with those of T-COPD. METHODS: A retrospective observational study that included consecutive patients seen at a specialized COPD clinic (2008-2021). The incidence of severe AECOPD that required hospital admission was studied. For the first AECOPD, the following variables were recorded: fever, coexistence of pneumonia, purulent sputum, eosinophil count, neutrophil to lymphocyte ratio, hypercapnia, and respiratory acidosis. Outcome variables were intensive care unit (ICU) admission, length of hospital stay, and mortality within 1 month of hospital admission. RESULTS: Of 1060 subjects, 195 (18.4%) belonged to the B-COPD group and 865 (81.6%) to the T-COPD group. During a follow-up of 67.9 (37.8-98.8) months, 75 (38.4%) patients in the B-COPD group and 319 (36.8%) in the T-COPD group suffered at least one severe AECOPD. The only difference between groups was in a higher risk of ICU admission for the T-COPD group. The incidence, characteristics, and the rest of the outcomes of AECOPD were similar for both groups. CONCLUSION: AECOPD are similar events for B-COPD and T-COPD and should be managed similarly.

Trajectories of Severe Exacerbations of Chronic Obstructive Pulmonary Disease and Their Relationship with Mortality Risk.

PURPOSE: Acute exacerbations of COPD (AECOPD) are important factors contributing to mortality risk. The rate of exacerbations varies overtime. An inconsistent pattern of exacerbation occurrence is a common finding. The mortality risk associated with such a pattern is not entirely clear. Our objective was to assess the risk of mortality associated with various possible patterns of AECOPD trajectories. METHODS: This is a multicenter historical cohort study. Four different exacerbation trajectories were defined according to the incidence of severe AECOPD requiring hospital admission 2 years before and after the date of the first visit to the respiratory clinic-Consistent non-exacerbators (NEx): no AECOPD before or after the index date; consistent exacerbators (Ex): at least one AECOPD both before and after the index date; converters to exacerbators (CONV-Ex): no exacerbations before and at least one AECOPD after the index date; converters to non-exacerbators (CONV-NEx): at least one AECOPD before the index date, and no exacerbations after said date. All-cause mortality risk for these trajectories was assessed. RESULTS: A total of 1713 subjects were included in the study: NEx: 1219 (71.2%), CONV-NEx: 225 (13.1%), CONV-Ex: 148 (8.6%), Ex: 121 (7.1%). After correcting for confounding variables, the group with the highest mortality risk was Ex. The CONV-Ex and CONV-Nex groups had a mortality risk between Ex and NEx, with no significant differences between them. CONCLUSION: Different possible trajectories of severe AECOPD before and after a first specialized consultation are associated with different mortality risks. An inconsistent pattern of exacerbations has a mortality risk between Ex and NEx, with no clear differences between CONV-Ex and CONV-NEx.

The Response to Biologics is Better in Patients with Severe Asthma Than in Patients with Asthma-COPD Overlap Syndrome.

Although biologics have demonstrated to be effective in T2-high asthma patients, there is little experience with these drugs in asthma-COPD overlap (ACO). The aim of this study was to compare the effectiveness of biologics in these two conditions. We included 318 patients (24 ACO and 297 asthma) treated with monoclonal antibodies and followed for at least 12 months. Omalizumab was the most frequently employed biologic agent both in patients with ACO and asthma. Asthma control test (ACT) scores after at least 12 months of biologic therapy were not significantly different between groups. The percentage of patients with ≥1 exacerbation and ≥1 corticosteroid burst was significantly higher in ACO patients (70.8 vs 27.3 and 83.3% vs 37.5%, respectively), whereas the percentage of "controlled" patients (with no exacerbations, no need for corticosteroids and ACT ≥ 20) was significantly lower (16.7% vs 39.7%). In conclusion, this report suggests that patients with ACO treated with biologics reach worse outcomes than asthma patients.

A new, three-dimensional approach to the GOLD COPD assessment tool.

BACKGROUND: The 2-dimensional, 4-quadrant 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD A-D assessment tool (GOLD2017) does not include lung function variables to classify patients into different risk groups. The previous 2011 tool (GOLD2011) classified cases in the upper-quadrants (higher risk groups) regardless of whether they had a history of exacerbations or worse lung function. We hypothesized that a modified, three-dimensional classification (GOLD3D) that separately includes assessment of lung function and exacerbations history would improve the ability to predict adverse events. METHODS: A total of 1303 COPD patients were included in a historical cohort study. The ability of GOLD3D to predict outcomes (all-cause death and hospitalizations due to severe exacerbation) was compared with GOLD2017 and GOLD2011. RESULTS: Mean follow-up was 45.0 ± 28.0 months. Two hundred and twenty-eight patients (17.5%) died and 337 (25.9%) subjects suffered at least a severe exacerbation that required hospital admission. The area under the receiver-operating characteristics curve for mortality prediction was slightly but significantly higher for GOLD3D than for GOLD2011. The area under the curve for prediction of severe exacerbations was significantly higher for GOLD3D than for GOLD2011 and GOLD2017. A worse ventilatory obstruction was associated in most cases with a higher mortality risk and a higher exacerbation risk for the GOLD2017 A-D groups. CONCLUSIONS: The proposed GOLD3D classification system upgrades the previous ones, and is advantageous in predicting future adverse events.

Efficacy of mepolizumab in usual clinical practice and characteristics of responders.

BACKGROUND: Severe eosinophilic asthma is a high-burden disease. Mepolizumab has been effective in several randomized clinical trials. However, such success might not be applicable to patients treated in usual clinical practice. The objectives of this article are to evaluate the efficacy of mepolizumab in severe uncontrolled eosinophilic asthma under usual clinical practice, and to determine characteristics associated with the response to this treatment. METHODS: We have conducted a retrospective, multicentre study, including all adult patients with severe uncontrolled eosinophilic asthma in Galicia, Spain, on whom mepolizumab treatment was started before June 2020, at least 6 months before the time of inclusion, and had received at least one dose of the drug. Patient characteristics, clinical data, respiratory function and comorbidities were collected at baseline and at the 6-month-follow-up. Responders and super-responders were defined according to clinical response and requirement of systemic corticosteroids. RESULTS: 122 patients (mean age 58 years old) were included. In the follow-up treatment 6 months later, 75.4% of the patients were well-controlled, displaying a significant reduction in blood eosinophil counts (p < 0.001), hospital admissions and disease exacerbations (p < 0.001), and had their systemic glucocorticosteroid dose significantly reduced (p < 0.001). The inhaled corticosteroid dose was also lowered (p < 0.01) after 6 months of treatment. Around two-thirds had a clinically significant increase in FEV1, 95% of the patients were considered responders and 43% super-responders. CONCLUSION: In routine clinical practice, mepolizumab is effective in patients with severe eosinophilic asthma and it has a good safety profile.

Phenotype-Guided Asthma Therapy: An Alternative Approach to Guidelines.

Despite recent advances in therapy, a substantial proportion of asthmatics remain not well controlled. The classical stepwise approach to pharmacological therapy in adult asthma recommends that treatment is progressively stepped up by increasing the inhaled corticosteroid (ICS) dose or by adding another controller medication- to achieve symptom control and reduce the risk of exacerbations, and stepped down after a period of control. In general, asthma guideline recommendations do not reflect that there are significant differences between ICS in terms of potency. Moreover, they do not consider efficacy and safety separately, incorrectly assuming that "low" and "high" dose categories inevitably correspond with low and high risk of systemic effects. Another point of criticism is the fact that guidelines do not take into account the inflammatory profile of the patient, although substantial groups of patients with mild and moderate asthma have little evidence of "T2-high" inflammation, and by extension are likely to show a poor response to ICS treatment. On the other hand, the latest version of the Global Initiative for Asthma (GINA) equally recommends regular ICS and ICS/formoterol as needed to prevent exacerbations in step 2 patients, without taking into consideration that the therapeutic objectives (exacerbations, symptoms) may differ between individual patients and that different goals may warrant distinct treatment strategies. In this review, we bring to the table several controversial issues concerning asthma treatment and suggest an alternative proposal that takes into consideration the potential side effects of high ICS doses, the patient's inflammatory profile and the therapeutic goals to be achieved.