Currently, and based on the development of relevant biologic therapies, T2-high is the most well-defined endotype of asthma. Although much progress has been made in elucidating T2-high inflammation ...pathways, no specific clinically applicable biomarkers for T2-low asthma have been identified. The therapeutic approach of T2-low asthma is a problem urgently needing resolution, firstly because these patients have poor response to steroids, and secondly because they are not candidates for the newer targeted biologic agents. Thus, there is an unmet need for the identification of biomarkers that can help the diagnosis and endotyping of T2-low asthma.
Ongoing investigation is focusing on neutrophilic airway inflammation mediators as therapeutic targets, including interleukin (IL)-8, IL-17, IL-1, IL-6, IL-23 and tumour necrosis factor-α; molecules that target restoration of corticosteroid sensitivity, mainly mitogen-activated protein kinase inhibitors, tyrosine kinase inhibitors and phosphatidylinositol 3-kinase inhibitors; phosphodiesterase (PDE)3 inhibitors that act as bronchodilators and PDE4 inhibitors that have an anti-inflammatory effect; and airway smooth muscle mass attenuation therapies, mainly for patients with paucigranulocytic inflammation.
This article aims to review the evidence for noneosinophilic inflammation being a target for therapy in asthma; discuss current and potential future therapeutic approaches, such as novel molecules and biologic agents; and assess clinical trials of licensed drugs in the treatment of T2-low asthma.
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.
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.
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.
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.
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 (F
= 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 (F
= 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.
Chronic respiratory diseases constitute a considerable part in the practice of pulmonologists and primary care physicians; spirometry is integral for the diagnosis and monitoring of these diseases, ...yet remains underutilized. The Air Next spirometer (NuvoAir, Sweden) is a novel ultra-portable device that performs spirometric measurements connected to a smartphone or tablet via Bluetooth®.
The objective of this study was to assess the accuracy and validity of these measurements by comparing them with the ones obtained with a conventional desktop spirometer. Two hundred subjects were enrolled in the study with various spirometric patterns (50 patients with asthma, 50 with chronic obstructive pulmonary disease and 50 with interstitial lung disease) as well as 50 healthy individuals.
For the key spirometric parameters in the interpretation of spirometry, i.e. FEV
, FVC, FEV
/FVC and FEF
, Pearson correlation and Interclass Correlation Coefficient were greater than 0.94, exhibiting perfect concordance between the two spirometers. Similar results were observed in an exploratory analysis of the subgroups of patients. Using Bland-Altman plots we have shown good reproducibility in the measurements between the two devices, with small mean differences for the evaluated spirometric parameters and the majority of measurements being well within the limits of agreement.
Our results support the use of Air Next as a reliable spirometer for the screening and diagnosis of various spirometric patterns in clinical practice.
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.
Idiopathic Pulmonary Fibrosis (IPF) represents a chronic lung disease with unpredictable course.
We aimed to investigate prognostic performance of complete blood count parameters in IPF. ...Treatment-naïve patients with IPF were retrospectively enrolled from two independent cohorts (derivation and validation) and split into subgroups (high and low) based on median baseline monocyte count and red cell distribution width (RDW).
Overall, 489 patients (derivation cohort: 300, validation cohort: 189) were analyzed. In the derivation cohort, patients with monocyte count ≥ 0.60 K/μL had significantly lower median FVC%pred 75.0, (95% CI 71.3-76.7) vs. 80.9, (95% CI 77.5-83.1), (P = 0.01) and DLCO%pred 47.5, (95% CI 44.3-52.3) vs. 53.0, (95% CI 48.0-56.7), (P = 0.02) than patients with monocyte count < 0.60 K/μL. Patients with RDW ≥ 14.1% had significantly lower median FVC%pred 75.5, (95% CI 71.2-79.2) vs. 78.3, (95% CI 76.0-81.0), (P = 0.04) and DLCO%pred 45.4, (95% CI 43.3-50.5) vs. 53.0, (95% CI 50.8-56.8), (P = 0.008) than patients with RDW < 14.1%. Cut-off thresholds from the derivation cohort were applied to the validation cohort with similar discriminatory value, as indicated by significant differences in median DLCO%pred between patients with high vs. low monocyte count 37.8, (95% CI 35.5-41.1) vs. 45.5, (95% CI 41.9-49.4), (P < 0.001) and RDW 37.9, (95% CI 33.4-40.7) vs. 44.4, (95% CI 41.5-48.9), (P < 0.001). Patients with high monocyte count and RDW of the validation cohort exhibited a trend towards lower median FVC%pred (P = 0.09) and significantly lower median FVC%pred (P = 0.001), respectively. Kaplan-Meier analysis in the derivation cohort demonstrated higher all-cause mortality in patients with high (≥ 0.60 K/μL) vs. low monocyte count (< 0.60 K/μL) HR 2.05, (95% CI 1.19-3.53), (P = 0.01).
Increased monocyte count and RDW may represent negative prognostic biomarkers in patients with IPF.
Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory disease with multisystemic manifestations. Studies either held on stable disease patients or during exacerbations have ...demonstrated that COPD is strongly related to venous thromboembolism and cardiovascular events. The aim of the present review of the literature was to provide an in-depth overview regarding the alterations of coagulation factors and prothrombotic changes generated in patients with stable COPD and during COPD exacerbations.
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.
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