Biologic agents licensed for severe asthma: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Six biologic agents are now approved for patients with severe asthma. This meta-analysis aimed to assess the efficacy and safety of licensed biologic agents in patients with severe asthma, including the recently approved tezepelumab. METHODS: We searched MEDLINE, Embase and CENTRAL to identify randomised controlled trials involving licensed biologics until 31 January 2023. We used random-effects meta-analysis models for efficacy, including subgroup analyses by individual agents and markers of T2-high inflammation (blood eosinophils and fractional exhaled nitric oxide), and assessed safety. RESULTS: 48 studies with 16 350 patients were included in the meta-analysis. Biologics were associated with a 44% reduction in the annualised rate of asthma exacerbations (rate ratio 0.56, 95% CI 0.51-0.62) and 60% reduction of hospitalisations (rate ratio 0.40, 95% CI 0.27-0.60), a mean increase in the forced expiratory volume in 1 s of 0.11 L (95% CI 0.09-0.14), a reduction in asthma control questionnaire by 0.34 points (95% CI -0.46--0.23) and an increase in asthma quality of life questionnaire by 0.38 points (95% CI 0.26-0.49). There was heterogeneity between different classes of biologics in certain outcomes, with overall greater efficacy in patients with T2 inflammation. Overall, biologics exhibited a favourable safety profile. CONCLUSIONS: This comprehensive meta-analysis demonstrated that licensed asthma biologics reduce exacerbations and hospitalisations, improve lung function, asthma control and quality of life, and limit the use of systemic corticosteroids, with a favourable safety profile. These effects are more prominent in patients with evidence of T2 inflammation.

Recent Advances of Artificial Intelligence Applications in Interstitial Lung Diseases.

Interstitial lung diseases (ILDs) comprise a rather heterogeneous group of diseases varying in pathophysiology, presentation, epidemiology, diagnosis, treatment and prognosis. Even though they have been recognized for several years, there are still areas of research debate. In the majority of ILDs, imaging modalities and especially high-resolution Computed Tomography (CT) scans have been the cornerstone in patient diagnostic approach and follow-up. The intricate nature of ILDs and the accompanying data have led to an increasing adoption of artificial intelligence (AI) techniques, primarily on imaging data but also in genetic data, spirometry and lung diffusion, among others. In this literature review, we describe the most prominent applications of AI in ILDs presented approximately within the last five years. We roughly stratify these studies in three categories, namely: (i) screening, (ii) diagnosis and classification, (iii) prognosis.

Effectiveness and quality of life in asthmatic patients treated with budesonide/formoterol via Elpenhaler® device in primary care. The "SKIRON" real world study.

Aim: Inhaled corticosteroid (ICS)/long-acting ß2 agonist (LABA) combination therapy is used for the effective control of asthma. Aim of this study was to collect data on the effectiveness, safety, quality of life, and patient satisfaction from a fixed dose combination of budesonide/formoterol administered with the Elpenhaler® device following 3-months' treatment.Methods: A 3-month real-life, multicentre, one-arm, prospective observational study (SKIRON study-NCT03055793) was conducted, using the following questionnaires: Asthma Control Questionnaire (ACQ-6) for asthma control assessment, MiniAQLQ questionnaire for QoL assessment, and Feeling of Satisfaction with Inhaler questionnaire (FSI-10) for patients' satisfaction with the inhaler device. Comorbidities and safety data were also recorded during the study.Results: We enrolled 1,174 asthmatic patients following standard clinical practice in primary care from 126 sites in urban and rural areas of Greece. The majority of patients (71.5%) had at least one comorbidity. A statistically significant improvement in the ACQ-6 score was noted at 3 months compared to the baseline evaluation (mean ± SD 2.19 ± 0.97 at baseline vs. 0.55 ± 0.56 at 3 months; mean change -1.64 (95%CI -1.69, -1.57), p < 0.0001). MiniAQLQ score was statistically and clinically significantly improved, compared to baseline, (4.55 ± 1.04 at baseline vs. 6.37 ± 0.64 at 3 months; mean change 1.82 (95%CI 1.75, 1.87), p < 0.0001). The mean FSI-10 score of 44.2 ± 5.4 indicated patient satisfaction and ease-of-use of the Elpenhaler® device.Conclusions: In this large real-world study of inadequately-controlled asthma patients in primary care settings, the treatment with budesonide/formoterol FDC with the Elpenhaler® device was associated with significant improvement in patients' asthma control and quality of life.

A Real-World Study on the Day and Night-Time Symptoms Among Greek COPD Patients Who Recently Initiated Treatment with Dual Bronchodilation: The DANICO Study.

Purpose: The rationale of this study was to investigate the prevalence of daily and night symptoms and quality of sleep in Greek COPD patients as a means to evaluate their response to treatment with the fixed dose combination of aclidinium/formoterol (administered through the Genuair® device). Patients and Methods: This study was a multicenter, nationwide, non-interventional, observational study in 2105 patients suffering from COPD, who have recently started treatment with aclidinium/formoterol. Patients were attending to two visits, one baseline and a final visit, 3 months later. Different variables have been collected on either the baseline or the final visit or both: demographics, vital sign measurements, COPD-related medical history parameters, comorbidities, COPD assessment test (CAT), COPD severity based on spirometry measurements, COPD stage based on the ABCD assessment approach proposed by the 2019 Global Initiative for Chronic Obstructive Lung Disease (GOLD), COPD treatment report, and severity of early-morning, daytime and night-time COPD-related symptoms. Reasons for prescribing aclidinium/formoterol, satisfaction of patients to the treatment, as well as their compliance have also been recorded. Results: After 3 months on aclidinium/formoterol, 50.1% of the patients experienced an improvement in their early-morning symptoms. Furthermore, 49.9% of them experienced an improvement in their daily symptoms, 44.9% improved their night-time symptoms and 43.2% reduced the frequency of overnight sleep disruptions due to COPD symptoms. These favorable outcomes apply mainly to GOLD Groups B-D. Treatment with aclidinium/formoterol improved on average the pre-bronchodilation FEV1% pred by 3.18%, the post-bronchodilation FEV1% pred by 2.78% and reduced CAT score by 5.22 points. Satisfaction with using aclidinium/formoterol across patients was high, as well as compliance to therapy. Conclusion: Aclidinium/formoterol provided significant benefits on the quality of life of COPD patients by reducing the morning, daytime and the night-time symptoms and symptom burden in GOLD Groups B-D, and activity impairment under real-life conditions in all GOLD ABCD groups.

Asthma and Tobacco Smoking.

Asthma is a prevalent chronic pulmonary condition with significant morbidity and mortality. Tobacco smoking is implicated in asthma pathophysiology, diagnosis, prognosis and treatment. Smokers display increased prevalence and incidence of asthma, but a causal association cannot be claimed using existing evidence. Second-hand smoking and passive exposure to tobacco in utero and early life have also been linked with asthma development. Currently, approximately one-fourth of asthma patients are smokers. Regular smokers with asthma might display accelerated lung function decline and non-reversible airflow limitation, making their distinction from chronic obstructive pulmonary disease patients challenging. Asthma patients who smoke typically have uncontrolled disease, as shown by increased symptoms, more exacerbations and impaired quality of life. On the other hand, smoking cessation improves lung function and asthma severity. Thus, asthma patients and their caregivers should be actively questioned about their smoking status at each medical encounter, and smoking cessation ought to be strongly encouraged both for patients with asthma and their close contacts. Smokers with asthma should be provided with comprehensive smoking cessation interventions on top of other anti-asthma medications.

Clinical relevance of circulating autoantibodies in idiopathic pulmonary fibrosis; A NAt hard to break.

Patients with idiopathic pulmonary fibrosis are screened for circulating autoantibodies as part of the initial interstitial lung disease workup. Management of seropositive idiopathic pulmonary fibrosis is currently considered no different than that of lone idiopathic pulmonary fibrosis. Emerging data however suggest that the former may possess distinct characteristics in terms of pathophysiology, histopathology, prognosis and amenability to immunomodulation. In that context, the aim of our study was to evaluate the influence of autoantibody status on: (i) the decline of forced vital capacity; (ii) the decline of diffusing capacity of lung for carbon monoxide; and (iii) 3-year survival; in a cohort of 102 idiopathic pulmonary fibrosis patients. In a pilot sub-study, we also sought to evaluate whether changes in antibody status during disease course affect the aforementioned parameters by potentially reflecting activity of the autoimmunity component of the pro-fibrotic mechanism.

Adherence and quality of life assessment in patients with asthma treatment with budesonide/formoterol via the Elpenhaler device: the COMPLETE study.

BACKGROUND: Asthma is a chronic inflammatory disease of the airways that causes recurring episodes of wheezing, breathlessness, chest tightness and coughing. Inhaled drugs on a daily basis are the cornerstone of asthma treatment, therefore, patient adherence is very important. METHODS: We performed a multicenter, open, non-interventional, observational, prospective study of 716 adult patients diagnosed with asthma receiving FDC (Fixed-dose combination) budesonide/formoterol via the Elpenhaler device. We assessed the adherence to treatment at 3 and 6 months (based on the MMAS-8: 8-item Morisky Medication Adherence Scale), the quality of life and change in forced expiratory volume in 1 s (FEV1) from baseline to follow-up. RESULTS: Approximately 80% of the patients showed medium to high adherence throughout the study. The mean (SD) MMAS-8 score at 6 months was 6.85 (1.54) and we observed a statistically significant shift of patients from the low adherence group to the high adherence group at 6 months. Moreover, after 6 months of treatment with FDC budesonide/formoterol, we observed an increase in the patients' quality of life that as expressed by a change 2.01 (95%CI 1.93-2.10) units in Mini AQLQ (p < 0.0001) that was more pronounced in the high adherence group. The same trend was also observed in terms of spirometry (mean FEV1 2.58 L (0.85) at the end of the study, increased by 220 mL from baseline) with a higher improvement in the medium and high adherence groups. CONCLUSIONS: Treatment with FDC of budesonide/formoterol via the Elpenhaler device was associated with improvement in asthma-related quality of life and lung function over 6 months that were more prominent in patients with higher adherence. TRIAL REGISTRATION: 2017-HAL-EL-74 (ClinicalTrials.gov Identifier: NCT03300076).

The Role of Digital Tools in the Timely Diagnosis and Prevention of Acute Exacerbations of COPD: A Comprehensive Review of the Literature.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the airways and lung parenchyma with multiple systemic manifestations. Exacerbations of COPD are important events during the course of the disease, as they are associated with increased mortality, severe impairment of health-related quality of life, accelerated decline in lung function, significant reduction in physical activity, and substantial economic burden. Telemedicine is the use of communication technologies to transmit medical data over short or long distances and to deliver healthcare services. The need to limit in-person appointments during the COVID-19 pandemic has caused a rapid increase in telemedicine services. In the present review of the literature covering published randomized controlled trials reporting results regarding the use of digital tools in acute exacerbations of COPD, we attempt to clarify the effectiveness of telemedicine for identifying, preventing, and reducing COPD exacerbations and improving other clinically relevant outcomes, while describing in detail the specific telemedicine interventions used.

The Diagnostic Role of Uric Acid to Creatinine Ratio for the Identification of Patients with Adverse Pulmonary Embolism Outcomes.

BACKGROUND: Uric acid (UA) is the final product of purine metabolism and a marker of oxidative stress that may be involved in the pathophysiology of cardiovascular and thromboembolic disease. The aim of the current study is to investigate the potential value of UA to creatinine ratio (UA/Cr) as a diagnostic tool for the outcome of patients admitted with acute pulmonary embolism (PE) and the correlations with other parameters. METHODS: We evaluated 116 patients who were admitted for PE in a respiratory medicine department. PE was confirmed with computed tomography pulmonary angiography. Outcomes evaluated were hospitalization duration, mortality or thrombolysis and a composite endpoint (defined as mortality or thrombolysis). Patients were assessed for PE severity with the PE Severity Index (PESI) and the European Society of Cardiology (ESC) 2019 risk stratification. RESULTS: The median (interquartile range) UA/Cr level was 7.59 (6.3-9.3). UA/Cr was significantly associated with PESI (p < 0.001), simplified PESI (p = 0.019), and ESC 2019 risk stratification (p < 0.001). The area under the curve (AUC) for prediction of 30-day mortality by UA/Cr was 0.793 (95% CI: 0.667-0.918). UA/Cr levels ≥7.64 showed 87% specificity and 94% negative predictive value for mortality. In multivariable analysis UA/Cr was an independent predictor of mortality (HR (95% CI): 1.620 (1.245-2.108), p < 0.001) and composite outcome (HR (95% CI): 1.521 (1.211-1.908), p < 0.001). Patients with elevated UA/Cr levels (≥7.64) had longer hospitalization (median (IQR) 7 (5-11) vs. 6 (5-8) days, p = 0.006)), higher mortality (27.3% vs. 3.2%, p = 0.001) and worse composite endpoint (32.7% vs. 3.4%, p < 0.001). CONCLUSION: Serum UA/Cr ratio levels at the time of PE diagnosis are associated with disease severity and risk stratification, and may be a useful biomarker for the identification of patients at risk of adverse outcomes.

Self-perceived quality of sleep among COPD patients in Greece: the SLEPICO study.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide accompanied by a substantial social and economic burden for the patient and the society. Poor sleep quality among COPD patients is frequently unnoticed and unaddressed by physicians and patients themselves, although it is a major source of further deterioration of these patients' quality of life. The aim of the present study was to record the quality of sleep in COPD patients among the Greek population and correlate these findings with various features of these patients, using the COPD and Asthma Sleep Impact Scale (CASIS). This was a cross-sectional observational study. Forty different variables (demographics, vital sign measurements, COPD-related medical history parameters, comorbidities, CASIS questionnaire results, COPD assessment test, COPD severity based on spirometry measurements, COPD stage based on the ABCD assessment approach, inhaled COPD treatment report) were collected from 3454 nation-wide COPD patients (Greece). The study sample consisted of COPD patients, mainly male (73%) with a median age of 69 years and a median BMI of 27.2. More than half of COPD patients (60.6%) suffered from moderate disease severity and 23.8% from severe disease, while less than half (42.1%) suffered from at least one exacerbation of the disease over the last year prior study enrollment. About 14% reported frequent to very frequent issues affecting their sleep quality, between a fourth and a third of them reported occasional night sleep disturbances, and at least half of them reported no or very infrequent problems in their night sleep. Our study indicates that the COPD assessment test (CAT) and the spirometry-based disease severity can predict the poorness in the quality of sleep (F2,3451 = 1397.5, p < 0.001, adj. R2 = 0.45) as assessed by CASIS score, and that the latter also correlates with age (ρ = 0.122, p < 0.001) and disease duration (ρ = 0.104, p < 0.001). On the contrary, there appears to be no correlation between sleep quality and number of exacerbations. Finally, untreated patients with COPD suffer from poorer quality of sleep compared to treated subjects, independently of the use of inhaled corticosteroids (F2,3451 = 21.65, p < 0.001). The results of the SLEPICO study show that increased age, prolonged disease duration, and especially CAT score ≥ 10, and severe COPD stage, might act as important indicators for deterioration in the quality of sleep, with potential consequences in the daily routine of those patients, thus urging potentially for further pharmacological interventions or modifications.

Recurrent bilateral lung infiltrates in a patient with ulcerative colitis.

In all cases of ILD in patients with UC, drug-induced pneumonitis should be excluded. In patients who receive both anti-TNF-α and mesalazine and develop drug-induced pneumonitis, it is quite difficult to differentiate which is the actual causing agent. https://bit.ly/3AnNJNN.

Prothrombotic state in patients with stable COPD: an observational study.

BACKGROUND: COPD patients have an increased risk of cardiovascular disease and venous thromboembolism. METHODS: This study aimed to investigate whether patients with stable COPD have a prothrombotic state compared to COPD-free smokers. We conducted an observational study comparing levels of: D-dimers, INR, aPTT, coagulation factors; fibrinogen, FII, FV, FVII, FVIII, FIX, FX and coagulation inhibitors; protein S, proteins C and antithrombin between stable COPD patients and control subjects. RESULTS: A total of 103 COPD patients and 42 controls with similar age, sex, current smoking status, comorbidity burden and cardiovascular risk met the inclusion criteria. Compared to controls, COPD patients had higher levels of D-dimers (median (interquartile range): 360 (230-600) ng·mL-1 versus 240 (180-400) ng·mL-1, p=0.001), fibrinogen (mean±sd: 399±82 mg·dL-1 versus 346±65 mg·dL-1, p<0.001), FII (122±22% versus 109±19%, p=0.004), FV (131±25% versus 121±19%, p=0.015), FVIII (143±32% versus 122±20%, p<0.001) and FX (111 (94-134)% versus 98 (88-107)%, p=0.002), and lower levels of protein S (95 (85-105)% versus 116 (98-121)%, p<0.001) and antithrombin (94.4±11.5% versus 102.3±13.2%, p=0.001). In the COPD group, patients with more severe airflow limitation and frequent exacerbations had significantly higher levels of FII, FV and FX, whereas patients with higher COPD assessment test score had significantly higher levels of FX and lower levels of protein S. CONCLUSION: Patients with stable COPD exhibited increased levels of key coagulation factors and decreased levels of coagulation inhibitors, namely protein S and antithrombin, compared to COPD-free smokers. Among COPD patients, increased levels of FII, FV and FX and decreased levels of protein S were found in patients with more severe disease.

Tocilizumab administration for the treatment of hospitalized patients with COVID-19: A systematic review and meta-analysis.

Tocilizumab has been repurposed against the 'cytokine storm' in the setting of coronavirus disease 2019 (COVID-19). Our aim was to evaluate the efficacy of tocilizumab in the management of hospitalized COVID-19 patients. We searched MEDLINE, CENTRAL and medRxiv for studies of tocilizumab in hospitalized COVID-19 patients. Primary objective was the effectiveness of tocilizumab on mortality. Secondary objectives included the need for invasive mechanical ventilation (IMV), composite endpoints of mortality or IMV and intensive care unit (ICU) admission or IMV, length of hospitalization and differences in mortality in subgroups (ICU and non-ICU patients and patients receiving or not receiving concomitant corticosteroids). We included 52 studies (nine randomized controlled trials [RCTs] and 43 observational) with a total of 27,004 patients. In both RCTs and observational studies, the use of tocilizumab was associated with a reduction in mortality; 11% in RCTs (risk ratio [RR] 0.89, 95% CI 0.82 to 0.96) and 31% in observational studies (RR 0.69, 95% CI 0.58 to 0.83). The need for IMV was reduced by 19% in RCTs (RR 0.81, 95% CI 0.71 to 0.93), while no significant reduction was observed in observational studies. Both RCTs and observational studies showed a benefit from tocilizumab on the composite endpoint of mortality or IMV. Tocilizumab improved mortality both in ICU and non-ICU patients. Reduction in mortality was evident in observational studies regardless of the use of systemic corticosteroids, while that was not the case in the RCTs. Tocilizumab was associated with lower mortality and other clinically relevant outcomes in hospitalized patients with moderate-to-critical COVID-19.