Can Treatable Traits Be the Approach to Addressing the Complexity and Heterogeneity of COPD?

the complexity of COPD implies the need to identify groups of patients with similar clinical characteristics and prognosis or treatment requirements. this is why much attention has been paid to identifying the different clinical phenotypes by investigating the clinical expression of the disease, and endotypes by studying the biological networks that enable and limit reactions. however, this approach is complicated because one endotype gives rise to one or more clinical characteristics, and clinical phenotypes can be derived from several endotypes. to simplify the approach, a new taxonomic classification of COPD based on the different causes (or etiotypes) has been proposed, but these etiotypes have not yet been validated. a simpler method is the so-called tractable traits approach, which is free from any designation of the disorder to be treated and does not present the criticality of using etiotypes. a large randomised controlled trial on using the treatable traits approach in COPD is still lacking. nevertheless, this approach is already applied by following the GOLD strategy. however, its application is complicated because several potentially treatable traits have been identified within the pulmonary domain, the extrapulmonary domain, and the behavioural/risk factor domain. In addition, the hierarchy of the dominant treatable traits has not yet been established, and they change over time both spontaneously and because of treatment. This means that the patients being treated according to the tractable traits approach must be constantly followed over time so that the therapy is focused on their temporal needs

Pharmacological management of COVID-19 patients with ARDS (CARDS): A narrative review

Coronavirus disease 2019 (COVID-19) is highly infectious. It has been highlighted that if not expertly and individually managed with consideration of the vasocentric features, a COVID-19 patient with an acute respiratory distress syndrome (CARDS) may eventually develop multiorgan failure. Unfortunately, there is still no definite drug for CARDS that is capable of reducing either short-term or long-term mortality and no specific treatments for COVID-19 exist right now. In this narrative review, based on a selective literature search in EMBASE, MEDLINE, Scopus, The Cochrane Library, Web of Science, and Google Scholar and ClinicalTrials.gov, we have examined the emerging evidence on the possible treatment of CARDS. Although numerous pharmacologic therapies to improve clinical outcomes in CARDS have been studied also in clinical trials, none have shown efficacy and there is great uncertainty about their effectiveness. There is still no recommendation for the therapeutic use of any specific agent to treat CARDS because no drugs are validated to have significant efficacy in clinical treatment of COVID-19 patients in large-scale trials. However, there exist a number of drugs that may be useful at least in some patients. The real challenge now is to link the right patient to the right treatment

Feasibility and results of awake thoracoscopic resection of solitary pulmonary nodules

BACKGROUND: General anesthesia with single-lung ventilation is considered mandatory for thoracoscopic pulmonary resection. We assessed in a randomized study the feasibility and results of awake thoracoscopic resection of solitary pulmonary nodules. METHODS: Between March 2001 and February 2003, 60 patients were randomized into two 30-patients arms: a general anesthesia arm entailing double-lumen intubation and thoracic epidural anesthesia (control group); and an awake arm entailing sole thoracic epidural anesthesia at T4-T5 (awake group). Anesthesia time; operative time; global operating room time; patient satisfaction with the anesthesia and technical feasibility scored into 4 grades (from 1 = poor to 4 = excellent); visual analog pain score (VAS), nursing care (number of patient calls per day), 24 hours changes in arterial oxygenation (DeltaPaO2), and hospital stay were assessed. RESULTS: There was no mortality. There was no difference in technical feasibility between the groups although 2 patients in the awake group required conversion to thoracotomy due to severe adhesions. Other 2 patients in each group required conversion due to unexpected lung cancer requiring lobectomy. Comparisons of awake versus control group results showed that in the awake group, anesthesia satisfaction score was greater (4 vs 3, p = 0.04), whereas DeltaPaO2 (-3 mm Hg vs -6.5 mm Hg, p = 0.002); nursing care (2.5 calls per day vs 4 calls per day, p = 0.0001), and hospital stay (2 days vs 3 days, p = 0.02) were significantly reduced. CONCLUSIONS: In our study, awake thoracoscopic resection of solitary pulmonary nodules proved safely feasible. It resulted in better patient satisfaction, less nursing care and shorter in-hospital stay than procedures performed under general anesthesi

Dexamethasone in patients hospitalized with COVID-19: Whether, when and to whom

A clinical interpretation of the Randomized Evaluation of COVID-19 Therapy (RECOVERY) study was performed to provide a useful tool to understand whether, when, and to whom dexamethasone should be administered during hospitalization for COVID-19. A post hoc analysis of data published in the preliminary report of the RECOVERY study was performed to calculate the person-based number needed to treat (NNT) and number needed to harm (NNH) of 6 mg dexamethasone once daily for up to 10 days vs. usual care with respect to mortality. At day 28, the NNT of dexamethasone vs. usual care was 36.0 (95%CI 24.9–65.1, p < 0.05) in all patients, 8.3 (95%CI 6.0–13.1, p < 0.05) in patients receiving invasive mechanical ventilation, and 34.6 (95%CI 22.1–79.0, p < 0.05) in patients receiving oxygen only (with or without noninvasive ventilation). Dexamethasone increased mortality compared with usual care in patients not requiring oxygen supplementation, leading to a NNH value of 26.7 (95%CI 18.1–50.9, p < 0.05). NNT of dexamethasone vs. usual care was 17.3 (95%CI 14.9–20.6) in subjects <70 years, 27.0 (95%CI 18.5–49.8) in men, and 16.2 (95%CI 13.2–20.8) in patients in which the onset of symptoms was >7 days. Dexamethasone is effective in male subjects < 70 years that require invasive mechanical ventilation experiencing symptoms from >7 days and those patients receiving oxygen without invasive mechanical ventilation; it should be avoided in patients not requiring respiratory support

Use of human airway smooth muscle in vitro and ex vivo to investigate drugs for the treatment of chronic obstructive respiratory disorders

Isolated airway smooth muscle has been extensively investigated since 1840 to understand the pharmacology of airway diseases. There has often been poor predictability from murine experiments to drugs evaluated in patients with asthma or chronic obstructive pulmonary disease (COPD). However, the use of isolated human airways represents a sensible strategy to optimise the development of innovative molecules for the treatment of respiratory diseases. This review aims to provide updated evidence on the current uses of isolated human airways in validated in vitro methods to investigate drugs in development for the treatment of chronic obstructive respiratory disorders. This review also provides historical notes on the pioneering pharmacological research on isolated human airway tissues, the key differences between human and animal airways, as well as the pivotal differences between human medium bronchi and small airways. Experiments carried out with isolated human bronchial tissues in vitro and ex vivo replicate many of the main anatomical, pathophysiological, mechanical and immunological characteristics of patients with asthma or COPD. In vitro models of asthma and COPD using isolated human airways can provide information that is directly translatable into humans with obstructive lung diseases. Regardless of the technique used to investigate drugs for the treatment of chronic obstructive respiratory disorders (i.e., isolated organ bath systems, videomicroscopy and wire myography), the most limiting factors to produce high-quality and repeatable data remain closely tied to the manual skills of the researcher conducting experiments and the availability of suitable tissue

Oral corticosteroids dependence and biologic drugs in severe asthma: Myths or facts? a systematic review of real‐world evidence

Airway inflammation represents an important characteristic in asthma, modulating airflow limitation and symptom control, and triggering the risk of asthma exacerbation. Thus, although corticosteroids represent the cornerstone for the treatment of asthma, severe patients may be dependent on oral corticosteroids (OCSs). Fortunately, the current humanised monoclonal antibodies (mAbs) benralizumab, dupilumab, mepolizumab, omalizumab, and reslizumab have been proven to induce an OCS‐sparing effect in randomized controlled trials (RCTs), thus overcoming the problem of OCS dependence in severe asthma. Nevertheless, a large discrepancy has been recognized between selected patients enrolled in RCTs and non‐selected asthmatic populations in real‐world settings. It is not possible to exclude that the OCS‐sparing effect of mAbs resulting from the RCTs could be different than the real effect resulting in clinical practice. Therefore, we performed a systematic review and correlation analysis to assess whether mAbs are effective in eliciting an OCS‐sparing effect and overcoming the OCS dependence in severe asthmatic patients in real‐world settings. Overall, real‐world studies support the evidence that OCS dependence is a real condition that, however, can be found only in a small number of really severe asthmatic patients. In most patients, the dependence on OCS can be related to modifying factors that, when adequately modulated, may lead to a significant reduction or suspension of OCS maintenance. Conversely, in severe asthmatics in whom OCS resistance is proved by a high daily dose intake, mAbs allow reversion of the OCS dependence, leading to the suspension of OCS therapy in most patients or >50% reduction in the daily OCS dose

HSV positivity in bronco-alveolar lavage fluid and clinical outcome in hospitalized patients

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Clinically Important Deterioration (CID) and Ageing in COPD: A Systematic Review and Meta-Regression Analysis According to PRISMA Statement

purpose: clinically important deterioration (CID) is a composite endpoint developed to quantify the impact of pharmacological treatment in clinical trials for chronic obstructive pulmonary disease (COPD), also showing a prognostic value. CID is defined as any of the following condition: forced expiratory volume in 1 s decrease ≥100 mL from baseline, and/or St. george's respiratory questionnaire total score increase ≥4-unit from baseline, and/or the occurrence of a moderate-to-severe exacerbation of COPD. although most COPD patients experience a clinical worsening as they get older, to date, no specific studies assessed the correlation between ageing and CID in COPD. therefore, the aim of this study was to investigate the impact of ageing on CID in COPD patients. patients and methods: data obtained from 55219 COPD patients were extracted from 17 papers, mostly post-hoc analyses. a pairwise meta-analysis and a meta-regression analysis were performed according to PRISMA-P guidelines to quantify the impact of pharmacological therapy on CID and to determine whether ageing might modulate the risk of CID in COPD patients. results: Inhaled treatments resulted generally effective in reducing the risk of CID in COPD (relative risk: 0.81, 95% confidence interval 0.79-0.84; P < 0.001). the meta-regression analysis indicated a trend toward significance (P = 0.063) in the linear relationship between age and the risk of CID. Of note, age significantly (P < 0.05) increased the risk of CID when associated with lower post-bronchodilator FEV1. these results were not affected by a significant risk of bias. conclusion: this quantitative synthesis suggests that inhaled therapy is effective in reducing the risk of CID in COPD, although such a protective effect may be affected in older patients with impaired lung function. further studies specifically designed on CID in COPD are needed to confirm these results