Cardiovascular disease remains the leading cause of death worldwide, yet classification still relies largely on anatomy, hemodynamics, and function, which can group patients with different underlying disease biology. Human studies across cardiovascular conditions now identify vascular, myocardial, metabolic, renal, hematologic, and peripheral processes that modify disease expression beyond conventional labels. Atherogenic particle burden, lipoprotein(a), clonal hematopoiesis, myocardial energetic and genetic abnormalities, chamber remodeling, dysfunctional adiposity, iron deficiency, skeletal muscle dysfunction, and cancer-associated cardiac wasting illustrate how similar phenotypes can arise from different substrates. These observations are supported to varying degrees by genetic, longitudinal, imaging, physiological, tissue, and interventional evidence, and their relative importance differs across patients and disease stages. Association with disease severity or outcome should therefore not be interpreted automatically as causal or therapeutically modifiable. Longitudinal phenotyping can clarify temporal relationships, while mechanistic studies should establish target engagement and the expected biological or physiological response. Clinical outcome trials must then determine whether modifying a candidate pathway improves patient-relevant outcomes. Mechanistically informed phenotyping may complement established cardiovascular classification by refining patient selection, distinguishing clinically meaningful substrates from associated signals, and supporting mechanism-directed therapeutic development where the evidence is sufficiently robust, rather than replacing established clinical disease labels.
Background: Obstructive sleep apnea (OSA) is a chronic respiratory disorder with nocturnal oxygen desaturation that is often associated with multisystemic sequelae such as hypertension, cardiovascular diseases, and increased morbidity and mortality. Obesity has been proposed as a modifiable risk factor; hence, the recent shift in focus to investigating anti-obesity medications for the management of OSA. Tirzepatide is the first U.S. FDA-approved pharmacotherapy for the treatment of moderate-to-severe OSA in adults with obesity to be utilized in combination with low caloric intake and physical activity, given its prior success in managing type 2 diabetes (T2D) and obesity. Methods: This narrative review evaluates tirzepatide and the SURMOUNT-OSA trial program as the key contemporary anchors for the pharmacological treatment of OSA in adults with concurrent obesity. Because the randomized evidence base currently comprises a single pivotal trial program, the review centers on SURMOUNT-OSA and its prespecified endpoints along with post hoc analyses, supplemented by observational, modeling, and mechanistic studies. Results: In the SURMOUNT-OSA program, tirzepatide produced randomized, placebo-controlled reductions in the apnea-hypopnea index, sleep apnea-specific hypoxic burden, body weight, and systemic inflammation. The program was designed around respiratory and metabolic endpoints rather than clinical events, so it cannot support conclusions about mortality, cardiovascular, or renal outcomes. Favorable signals for those events, including all-cause mortality, major adverse kidney events, and major adverse cardiovascular events, come only from nonrandomized observational cohorts and are best regarded as directional and exploratory rather than definitive. Conclusions: Tirzepatide may help frame OSA as a multifactorial and partially metabolically treatable disease and may represent a clinically meaningful expansion of treatment options alongside, rather than as a replacement for, established mechanical and procedural therapies. The available evidence is anchored in a single phase 3 trial program and limited by short follow-up and the absence of definitive comparative and long-term outcome data. Long-term durability of effect after discontinuation, generalizability beyond the SURMOUNT-OSA-eligible population, OSA-specific economic analysis, and head-to-head comparisons against CPAP remain the principal unsettled questions requiring dedicated long-term studies before firm clinical recommendations can be made.
Background: the widespread use of e-cigarettes (e-cigs) has raised significant public health concerns, particularly regarding the physical characteristics of the emitted aerosol. This pilot study addresses this gap by quantitatively assessing particulate matter (PM) emissions from e-cigs in a real-world indoor environment. Methods: using a portable optical particle counter (AirBeam3), we measured PM1, PM2.5, and PM10 concentrations during a round-trip walk along low- and heavy-traffic roads, and inside a bar with three individuals who were vaping. Results: results show that indoor e-cig use was associated with a marked increase in PM levels. The average PM2.5 concentration inside the bar with vapers was 28.8 µg/m³, with a peak of 84.7 µg/m³, which is 6.5 times higher than on a low-traffic street and 3.1 times higher than on a heavy-traffic street. Conclusions: we conclude that PM from e-cigs in indoor settings markedly deteriorates air quality. While this study cannot quantify direct health risks, these findings support precautionary considerations for extending indoor smoking bans to public places.
Background: The healthcare sector is a major contributor to greenhouse gas emissions, prompting an urgent need for environmentally sustainable practices. Chronic Obstructive Pulmonary Disease (COPD) management presents unique challenges in this context due to the frequent use of metered-dose inhalers containing high global warming potential propellants and the resource-intensive nature of acute exacerbations. Methods: This expert consensus paper explores how COPD care can be optimized to reduce environmental impact, while maintaining high standards of clinical effectiveness. We examine the patient journey, adherence patterns, and therapeutic strategies, including the role of single-inhaler triple therapy in preventing exacerbation, as determinants of healthcare-related emissions. Results: The potential of dry powder inhalers, accurate diagnosis, patient engagement, and sustained disease stability are highlighted as levers for environmentally sustainable care. We advocate for the integration of environmental impact as a formal outcome in randomized controlled trials, supported by standardized Life Cycle Assessment methodologies. Conclusions: Our findings suggest that environmentally conscious COPD management is not only possible but may enhance clinical outcomes and system sustainability.
Background: Severe asthma patients receiving biologic therapy require accurate functional assessment and longitudinal monitoring. Spirometry and impulse oscillometry (IOS) may provide complementary information on lung function. The aim of this study was to compare spirometry and IOS in severe asthma patients treated with biologics, evaluating their concordance and clinical relevance, and to assess longitudinal changes in asthma control, oral corticosteroid (OCS) use, exacerbations, and healthcare utilization over 18 months. Methods: In this real-world dual-centre longitudinal study, 40 patients with severe asthma treated with biologic therapy underwent spirometry and IOS at baseline and after 6, 12, and 18 months. Functional findings were compared between the two techniques and correlated with asthma control, OCS use, exacerbations, hospitalizations, and healthcare utilization. Results: Significant clinical improvement was observed over 18 months, with reductions in exacerbations, hospitalizations, healthcare utilization and OCS use, alongside improved ACT scores. FEF25–75% showed partial functional improvement and significant correlations with IOS indices, particularly R5–R20 (r=−0.52 to −0.65) and AX (r=−0.30 to −0.54), supporting the complementary role of oscillometry in longitudinal assessment. Conclusions: Biologic therapy significantly reduced the clinical burden of severe asthma. IOS may provide complementary information alongside spirometry for longitudinal functional monitoring in real-life setting.
