Search Results (32)

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown aetiology. Evidence on the progression of idiopathic pulmonary fibrosis (IPF) following the introduction of antifibrotic therapies still indicates a generally poor prognosis. IPF is associated with both respiratory and non-respiratory comorbidities, which can worsen symptoms and impact overall survival. Background/Objectives: The study aimed to investigate the effect of these comorbidities on the early and permanent discontinuation of pirfenidone or nintedanib in IPF patients. Methods: In this single-centre retrospective study, 101 patients diagnosed with IPF according to ATS/ERS/JRS/ALAT guidelines were treated with AFT. Clinical data were collected at 12 months prior to and up to 24 months following treatment initiation, including age, gender, smoking history, and the presence of respiratory and non-respiratory comorbidities. Results: The data showed that 21 patients (20.8%) discontinued treatment within the first 12 months. Additionally, pre-treatment comorbidities were not statistically correlated with the suspension of antifibrotic treatment. Among the overall cohort, 77 patients (76.2%) had at least one comorbidity and 27 (26.7%) had three or more comorbidities. Notably, 24 (23.8%) had respiratory comorbidities, while 75 (74.3%) had non-respiratory comorbidities. Conclusions: This real-life study emphasises the complexities involved in managing IPF, particularly regarding adherence to treatment when significant comorbidities are present. The evidence suggests that in patients with IPF, pre-treatment respiratory or non-respiratory conditions do not affect AFT discontinuation. Full article

In severe asthma, symptoms are unstable despite intensive treatment based on high doses of inhaled corticosteroids and on-demand use of oral corticosteroids. Although, recently, various biological agents related to Th2 cytokines have been added to intensive controller medications for severe asthma, a significant progress has not been observed in the management for symptoms (dyspnea, wheezing and cough). Medical treatment focused on Type 2 inflammation is probably insufficient to maintain good long-term management for severe asthma. Airway eosinophilia and decreased reversibility in forced expiratory volume in 1 second (FEV₁) are listed as major predictors for exacerbation-prone asthma. However, it is generally considered that asthma is complex and heterogeneous. It is necessary to establish precision medicine using treatable traits based on a multidimensional approach related to asthma. Since phospholipids generate lysophospholipids and arachidonic acid by phospholipases, lysophospholipids can be associated with the pathogenesis of this disease via action on smooth muscle, endothelium, and epithelium in the airways. Lysophosphatidic acid (LPA), lysophosphatidylcholine (LPC), and sphingosine 1-phosphate (S1P) are increased in bronchoalveolar fluid after allergen challenge. LPA, LPC, and S1P recruit eosinophils to the lungs and cause β₂-adrenergic desensitization. LAP and S1P cause contraction and hyperresponsiveness in airway smooth muscle. Moreover, lysophosphatidylserine and S1P are associated with the allergic reaction related to IgE/FcεRI in mast cells. Lysophospholipid action is probably comprised of corticosteroid resistance and is independent of Type 2 inflammation, and may be corelated with oxidative stress. Lysophospholipids may be a novel molecular target in advancing the management and treatment of asthma. This review discusses the clinical relevance of lysophospholipids in asthma. Full article

Autoimmune diseases are among the most prevalent diseases across the world with genetic and environmental factors that contribute to their etiology. Because the exact causes of autoimmune diseases are largely unknown, a Mendelian randomization (MR) approach is used here to examine the potential causal association between gene expression levels and disease risk across various tissues. Specifically, this study focuses on six autoimmune diseases including Crohn’s disease, ulcerative colitis, rheumatoid arthritis, multiple sclerosis, type 1 diabetes mellitus, and systemic lupus erythematosus. Several of these diseases are currently treatable with immunosuppressants that target specific genes, such as TNF-alpha, IL-23, CD20, and more. In this study, a two-sample MR analysis is performed with multitissue expression quantitative trait loci (eQTLs) and large-scale genome-wide association studies to investigate how gene expression can influence the risk of developing these diseases. Our results show that genes HLA-DQA1/2, HLA-DRB1/6, HLA-DQB2, C4A, CYP21A2, and HLA-DQB1-AS1 have a high causal effect across several diseases and tissues, and almost all of these findings originate from the major histocompatibility complex (MHC) region on Chromosome 6. Our findings support the current knowledge of genes associated with these diseases while also revealing novel genes that can be used for drug therapies in the future. Although several drug therapies currently exist to treat this selection of autoimmune diseases, we provide further insights into the main, common pathways responsible for autoimmune disease pathogenesis and discuss novel genes that lack research focus. Full article

Background: Explanations provided by healthcare professionals contribute to patient beliefs. Little is known about how healthcare professionals explain chronic breathlessness to people living with this adverse sensation. Methods: A purpose-designed survey disseminated via newsletters of Australian professional associations (physiotherapy, respiratory medicine, palliative care). Respondents provided free-text responses for their usual explanation and concepts important to include, avoid, or perceived as difficult to understand by recipients. Content analysis coded free text into mutually exclusive categories with the proportion of respondents in each category reported. Results: Respondents (n = 61) were predominantly clinicians (93%) who frequently (80% daily/weekly) conversed with patients about breathlessness. Frequent phrases included within usual explanations reflected breathlessness resulting from medical conditions (70% of respondents) and physiological mechanisms (44%) with foci ranging from multifactorial to single-mechanism origins. Management principles were important to include and phrases encouraging maladaptive beliefs were important to avoid. The most frequent difficult concept identified concerned inconsistent relationships between oxygenation and breathlessness. Where explanations included the term ’oxygen’, a form of cognitive shortcut (heuristic) may contribute to erroneous beliefs. Conclusions: This study presents examples of health professional explanations for chronic breathlessness as a starting point for considering whether and how explanations could contribute to adaptive or maladaptive breathlessness beliefs of recipients. Full article

Background: Indirect comparison among biologics in severe asthma (SA) is a challenging but desirable goal for clinicians in real life. The aim of the study is to define characteristics of a biologic-treated T2-driven-SA population and to evaluate the effectiveness of biologic treatments in a real-world setting by variation in intra/inter-biologic parameters in an up to 4-year follow-up. Methods: Demographic, clinical, functional, and biological characteristics were evaluated retrospectively in 104 patients recruited until July 2022 at baseline (T0) and over a maximum of 4 years (T4) of biologic therapy (omalizumab/OmaG = 41, from T0 to T4, mepolizumab/MepoG = 26, from T0 to T4, benralizumab/BenraG = 18, from T0 to T2, and dupilumab/DupiG = 19, from T0 to T1). Variations of parameters using means of paired Delta were assessed. Results: At baseline, patients had high prevalence of T2-driven comorbidities, low asthma control test (ACT mean 17.65 ± 4.41), impaired pulmonary function (FEV₁ 65 ± 18 %pred), frequent exacerbations/year (AEs 3.5 ± 3), and OCS dependence (60%). DupiG had lower T2 biomarkers/comorbidities and AEs, and worse FEV₁ (57 ± 19 %pred) compared to other biologics (p < 0.05). All biologics improved ACT, FEV₁%, FVC%, AEs rate, and OCS use. FEV₁% improved in MepoG and BenraG over the minimal clinically important difference and was sustained over 4 years in OmaG and MepoG. A significant RV reduction in OmaG (T4) and DupiG (T1), and BenraG normalization (T2) of airflow limitation were found. We observed through inter-biologic parameters pair delta variation comparison a significant nocturnal awakenings reduction in BenraG vs. OmaG/MepoG, and neutrophils reduction in BenraG/DupiG vs. OmaG. Conclusions: Indirect comparison among biologics unveils clinical and functional improvements that may mark a different effectiveness. These results may highlight the preference of a single biologic compared to another with regard to specific treatable traits. Full article

Different factors, not limited to the lung, influence the progression of ILDs. A “treatable trait” strategy was recently proposed for ILD patients as a precision model of care to improve outcomes. However, no data have been published so far on the prevalence of TTs in ILD. A prospective, observational, cohort study was conducted within the ILD Program at the IRCCS Humanitas Research Hospital (Milan, Italy) between November 2021 and November 2023. TTs were selected according to recent literature and assigned during multidisciplinary discussion (MDD) to one of the following categories: pulmonary, etiological, comorbidities, and lifestyle. Patients were further divided into four groups according to their post-MDD diagnosis: idiopathic ILD, sarcoidosis, connective tissue disease–ILD, and other ILD. The primary study outcome was the prevalence of each TT in the study population. A total of 116 patients with ILD [63.9% male; median (IQR) age: 69 (54–78) years] were included in the study. All the TTs identified in the literature were found in our cohort, except for intractable chronic cough. We also recognized differences in TTs across the ILD groups, with less TTs in patients with sarcoidosis. This analysis provides the first ancillary characterization of TTs in ILD patients in a real setting to date. Full article

Introduction: Long COVID (LC) is a global public health crisis affecting more than 70 million people. There is emerging evidence of different pathophysiological mechanisms driving the wide array of symptoms in LC. Understanding the relationships between mechanisms and symptoms helps in guiding clinical management and identifying potential treatment targets. Methods: This was a mixed-methods systematic review with two stages: Stage one (Review 1) included only existing systematic reviews (meta-review) and Stage two (Review 2) was a review of all primary studies. The search strategy involved Medline, Embase, Emcare, and CINAHL databases to identify studies that described symptoms and pathophysiological mechanisms with statistical analysis and/or discussion of plausible causal relationships between mechanisms and symptoms. Only studies that included a control arm for comparison were included. Studies were assessed for quality using the National Heart, Lung, and Blood Institute quality assessment tools. Results: 19 systematic reviews were included in Review 1 and 46 primary studies in Review 2. Overall, the quality of reporting across the studies included in this second review was moderate to poor. The pathophysiological mechanisms with strong evidence were immune system dysregulation, cerebral hypoperfusion, and impaired gas transfer in the lungs. Other mechanisms with moderate to weak evidence were endothelial damage and hypercoagulation, mast cell activation, and auto-immunity to vascular receptors. Conclusions: LC is a complex condition affecting multiple organs with diverse clinical presentations (or traits) underpinned by multiple pathophysiological mechanisms. A ‘treatable trait’ approach may help identify certain groups and target specific interventions. Future research must include understanding the response to intervention based on these mechanism-based traits. Full article

Background: The recognition of comorbidities is relevant for asthma management, especially if these conditions/diseases are treatable traits such as anxiety. This study aimed to explore the associations between asthma severity and child and parent asthma-related anxiety and to recognize the most common specific fears. Methods: This cross-sectional study consisted of 150 parents and their children diagnosed with asthma, and was conducted at the Pediatric Clinic of the University Hospital Center Split in Croatia. All children, from ages 3 to 17 years, underwent a thorough clinical examination. A total of 150 parents and 108 children filled out an asthma-related anxiety questionnaire in paper form. Results: Parents of children with moderate and severe asthma had higher asthma-related anxiety due to restrictions related to asthma symptoms (p = 0.032), and children diagnosed with moderate and severe asthma had greater anxiety due to restrictions related to asthma symptoms than children diagnosed with mild asthma (p = 0.004). Children’s anxiety was the highest when they experienced an asthmatic attack during physical activity (PA), and they fear that they will not be successful in sports or dancing due to asthma. Parents commonly reported the fear of an asthma attack without warning signs (p < 0.001), fear of drug side effects (p < 0.001), fear of absence from school (p = 0.006), and fear of an asthma attack during PA (p < 0.001). Conclusions: The current study reports findings of increased parental levels of anxiety when compared to their children, related to fear of an asthma attack occurring without warning signs, fear of side effects and fear of absence from school, as well as the fear of an asthma attack occurring during sports activities. When assessing individual items on anxiety associated with asthma, children most commonly reported concern related to physical activity. Full article

Streptococcal toxic shock syndrome (STTS) is a critical medical emergency marked by high morbidity and mortality, necessitating swift awareness, targeted treatment, and early source control due to its rapid symptom manifestation. This report focuses on a cohort of 13 patients admitted to Vall d’Hebron University Hospital Intensive Care Unit, Barcelona, from November 2022 to March 2023, exhibiting invasive Streptococcus pyogenes infections and meeting institutional sepsis code activation criteria. The primary infections were community-acquired pneumonia (61.5%) and skin/soft tissue infection (30.8%). All patients received prompt antibiotic treatment, with clinical source control through thoracic drainage (30.8%) or surgical means (23.1%). Organ support involved invasive mechanical ventilation, vasopressors, and continuous renal replacement therapy as per guidelines. Of note, 76.9% of patients experienced septic cardiomyopathy, and 53.8% required extracorporeal membrane oxygenation (ECMO). The study identified three distinct phenotypic profiles—hyperinflammatory, low perfusion, and hypogammaglobulinemic—which could guide personalized therapeutic approaches. STTS, with a mean SOFA score of 17 (5.7) and a 53.8% requiring ECMO, underscores the need for precision medicine-based rescue therapies and sepsis phenotype identification. Integrating these strategies with prompt antibiotics and efficient source control offers a potential avenue to mitigate organ failure, enhancing patient survival and recovery in the face of this severe clinical condition. Full article

Extracellular lysophospholipids (lysophosphatidic acid, lysophosphatidylcholine, sphingosine 1-phosphate, etc.), which are synthesized from phospholipids in the cell membrane, act as lipid mediators, and mediate various cellular responses in constituent cells in the respiratory system, such as contraction, proliferation, migration, and cytoskeletal organization. In addition to these effects, the expression of the adhesion molecules is enhanced by these extracellular lysophospholipids in pulmonary endothelial cells. These effects are exerted via specific G protein-coupled receptors. Rho, Ras, and phospholipase C (PLC) have been proven to be their signaling pathways, related to Ca²⁺ signaling due to Ca²⁺ dynamics and Ca²⁺ sensitization. Therefore, lysophospholipids probably induce pulmonary vascular remodeling through phenotype changes in smooth muscle cells, endothelial cells, and fibroblasts, likely resulting in acute respiratory distress syndrome due to vascular leak, pulmonary hypertension, and pulmonary fibrosis. Moreover, lysophospholipids induce the recruitment of inflammatory cells to the lungs via the enhancement of adhesion molecules in endothelial cells, potentially leading to the development of asthma. These results demonstrate that lysophospholipids may be novel therapeutic targets not only for injury, fibrosis, and hypertension in the lung, but also for asthma. In this review, we discuss the mechanisms of the effects of lysophospholipids on the respiratory system, and the possibility of precision medicine targeting lysophospholipids as treatable traits of these diseases. Full article

Pleural mesothelioma is an aggressive disease with diffuse nature, low median survival, and prolonged latency presenting difficulty in prognosis, diagnosis, and treatment. Here, we review all these aspects to underline the progress being made in its investigation and to emphasize how much work remains to be carried out to improve prognosis and treatment. Full article

(1) Background: Most controlled trials of cognitive behavior therapy (CBT) in people living with chronic obstructive pulmonary disease (COPD) have targeted anxiety and depression. (2) Methods: This pragmatic randomized controlled trial explored whether a comprehensive pulmonary rehabilitation program (CPRP) with CBT for breathlessness or social group control (CPRP + SC) significantly improved health outcomes. (3) Results: People with moderate-to-severe COPD were block randomized (CPRP + CBT n = 52 or CPRP + SC n = 49). Primary outcomes (Hospital Anxiety and Depression scale (HADs), six-minute walk distance (6MWD)) and secondary outcomes (breathlessness, quality of life and habitual physical activity) were assessed before and 1, 6 and 12 months post intervention. Between-group differences were calculated with mixed models for each time point to baseline (intention to treat (ITT)). Participants (n = 101, mean ± SD age 70 ± 8.5 years, 54 (53%) males, FEV₁% pred 47.7 ± 16.3) were similar between groups. Post intervention, primary outcomes did not differ significantly between groups at 1 (6MWD mean difference −7.5 [95% CI −34.3 to 19.4], HADs-A −0.3 [−1.4 to 0.9], HADs-D 0.2 [−0.8 to 1.3]), 6 (6MWD −11.5 [−38.1 to 15.1], HADs-A 1.1 [0.0 to 2.2], HADs-D 0.2 [−0.9 to 1.3]), or 12 months (6MWD −3.8 [−27.2 to 19.6], HADS-A −0.4 [−1.5 to 0.6], HADs-D −0.7 [−1.7 to 0.4]). (4) Conclusions: In this cohort, combining CBT with a CPRP did not provide additional health benefits beyond those achieved by a standard CPRP. Full article

The astounding number of genetic variants revealed in the 15 years of genome-wide association studies of asthma has not kept pace with the goals of translational genomics. Moving asthma diagnosis from a nonspecific umbrella term to specific phenotypes/endotypes and related traits may provide insights into features that may be prevented or alleviated by therapeutical intervention. This review provides an overview of the different asthma endotypes and phenotypes and the genomic findings from asthma studies using patient stratification strategies and asthma-related traits. Asthma genomic research for treatable traits has uncovered novel and previously reported asthma loci, primarily through studies in Europeans. Novel genomic findings for asthma phenotypes and related traits may arise from multi-trait and specific phenotyping strategies in diverse populations. Full article

People with asthma tend to be less physically active and more sedentary than people without asthma. This narrative review aimed to present key considerations when addressing physical inactivity and sedentary behaviour in people with asthma by identifying barriers and facilitators, determinants and correlates, and intervention approaches. Using a search strategy, electronic databases were searched for relevant studies. Data extracted from studies were qualitatively synthesised. A total of 26 studies were included in the review. Six studies reported asthma symptoms as a barrier to physical activity, while four studies reported having a supportive network as a physical activity facilitator. Across studies, physical activity correlates/determinants were pulmonary function, exercise capacity, body mass index, dyspnoea, psychological health, and asthma control. Interventions that effectively improved physical activity in the short term were a step-based prescription programme, a weight loss programme incorporating aerobic and resistance training, and a weight loss lifestyle intervention, while a high-intensity interval training pulmonary rehabilitation program was effective in the long term. The collective findings suggest that a personalised physical activity programme incorporating different strategies is needed. There was minimal evidence to provide recommendations to optimise sedentary behaviour in asthma, and more research is needed on the topic. Full article

Cardiovascular diseases (CVD) are among the leading causes of death worldwide. Many lines of evidence suggest that the disturbances in circadian rhythm are responsible for the development of CVDs; however, circadian misalignment is not yet a treatable trait in clinical practice. The circadian rhythm is controlled by the central clock located in the suprachiasmatic nucleus and clock genes (molecular clock) located in all cells. Dyslipidaemia and vascular inflammation are two hallmarks of atherosclerosis and numerous experimental studies conclude that they are under direct influence by both central and molecular clocks. This review will summarise the results of experimental studies on lipid metabolism, vascular inflammation and circadian rhythm, and translate them into the pathophysiology of atherosclerosis and cardiovascular disease. We discuss the effect of time-respected administration of medications in cardiovascular medicine. We review the evidence on the effect of bright light and melatonin on cardiovascular health, lipid metabolism and vascular inflammation. Finally, we suggest an agenda for future research and recommend on clinical practice. Full article